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{
"3a457": {
"substrates": {
"alfentanil": [
"Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance? [ PMID 8484504 ] Kharasch ED, Thummel KE. Anesth Analg 1993;76:1033-1039."
],
"alprazolam": [
"Alprazolam is another substrate for human cytochrome P450-3A isoforms. [ PMID 9617989 ] Venkatakrishnan K, Greenblatt DJ, von Moltke LL, Shader RI. JClin Psychopharmacol 1998 Jun;18(3):256."
],
"amlodipine": [
"Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4. [ PMID 11145223 ] Katoh M, Nakajima M, Yamazaki H, Yokoi T. Pharm Res. 2000 Oct;17(10):1189-97."
],
"aprepitant": [
"Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. [ PMID 14973304 ] Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA. J Clin Pharmacol. 2004 Mar;44(3):215-23.",
"Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. [ PMID 12891225 ] Majumdar AK, McCrea JB, Panebianco DL, Hesney M, Dru J, Constanzer M, Goldberg MR, Murphy G, Gottesdiener KM, Lines CR, Petty KJ, Blum RA. Clin Pharmacol Ther. 2003 Aug;74(2):150-6.",
"Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting. [ PMID 15562136 ] Massaro AM, Lenz KL. Ann Pharmacother. 2005 Jan;39(1):77-85."
],
"aripiprazole": [
"Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. [ PMID 15257633 ] Swainston Harrison T, Perry CM. Drugs. 2004;64(15):1715-36."
],
"astemizole": [
"Cardiac actions of antihistamines. [ PMID 8725389 ] Woosley RL. Annu Rev Pharmacol Toxicol 1996;36:233-252.",
"Systemic antifungal agents. Drug interactions of clinical significance. [ PMID 9512916 ] Albengres E, Le Louet H, Tillement JP. Drug Saf 1998 Feb;18(2):83-97.",
"Drug interactions with the nonsedating antihistamines. [ PMID 9225677 ] Ament PW, Paterson A. Am Fam Physician 1997 Jul;56(1):223-23."
],
"atorvastatin": [
"Effect of itraconazole on the pharmacokinetics of atorvastatin. [ PMID 9695720 ] Kantola T, Kivisto KT, Neuvonen PJ. Clin Pharmacol Ther 1998 Jul;64(1):58-65."
],
"azithromycin": [
""
],
"boceprevir": [
""
],
"buspirone": [
"Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. [ PMID 9333111 ] Kivisto KT, Lamberg TS, Kantola T, Neuvonen PJ. Clin Pharmacol Ther 1997 Sep;62(3):348-354."
],
"eplerenone": [
"Involvement of CYP3A in the metabolism of eplerenone in humans and dogs: differential metabolism by CYP3A4 and CYP3A5. [ PMID 12433801 ] Cook CS, Berry LM, Kim DH, Burton EG, Hribar JD, Zhang L. Drug Metab Dispos. 2002 Dec;30(12):1344-51."
],
"ergotamine": [
""
],
"caffeine": [
"Specificity of Substrate and Inhibitor Probes for Human Cytochromes P450 1A1 and 1A2. [ PMID 8474022 ] Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, and Tukey RH. J Pharmacol Exp Ther 265(1):401-407, 1993."
],
"cerivastatin": [
"Metabolism of cerivastatin by human liver microsomes in vitro. [ PMID 9172950 ] Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M. Drug Metab Dispos. 1997 Mar;25(3):321-31."
],
"chloramphenicol": [
"Chloramphenicol Is a Potent Inhibitor of Cytochrome P450 Isoforms CYP2C19 and CYP3A4 in Human Liver Microsomes. [ PMID 14576103 ] Park JY, Kim KA, Kim SL. Antimicrob Agents Chemother. 2003 Nov;47(11):3464-9."
],
"chlorpheniramine": [
""
],
"cilostazol": [
"Cilostazol: a review of its use in intermittent claudication. Chapman TM, Goa KL. Am J Cardiovasc Drugs. 2003;3(2):117-38."
],
"cinacalcet": [
"Pharmacokinetics of cinacalcet hydrochloride when administered with ketoconazole. [ PMID 17518508 ] Harris RZ, Salfi M, Sullivan JT, Padhi D. Clin Pharmacokinet. 2007;46(6):495-501."
],
"cisapride": [
"Cisapride and fatal arrhythmia. [ PMID 8657260 ] Wysowski DK, Bacsanyi J. Eng J Med 1996;335;290-291."
],
"clarithromycin": [
"Oxidative metabolism of clarithromycin in the presence of human liver microsomes. Major role for the cytochrome P4503A (CYP3A) subfamily. [ PMID 9152603 ] Rodrigues AD, Roberts EM, Mulford DJ, Yao Y, Ouellet D. Metab Dispos 1997 May;25(5):623-630."
],
"cocaine": [
""
],
"codeine": [
"Microsomal codeine N-demethylation: Cosegregation with cytochrome P4503A4 activity. [ PMID 8818573 ] Caraco Y, Tateishi T, Guengerich FP, Wood AJJ. Metab Dispos 1996;24(7):761-764."
],
"cyclosporine": [
"The role of cytochromes P-450 in cyclosporine metabolism. [ PMID 2277139 ] Watkins PB. Am Acad Dermatol 1990 Dec;23(6 Pt 2):1301-1309.",
"Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. [ PMID 3378384 ] Kronbach T, Fischer V, Meyer UA. Clin Pharmacol Ther 1988 Jun;43(6):630-635.",
"Exacerbation of cyclosporine toxicity by concomitant administration of erythromycin. [ PMID 3544386 ] Jensen CW, Flechner SM, Van Buren CT, Frazier OH, Cooley DA, Lorber MI, Kahan BD. Transplantation 1987 Feb;43(2):263-270.",
"Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients. [ PMID 1424421 ] Turgeon DK, Normolle DP, Leichtman AB, Annesley TM, Smith DE, Watkins PB. Clin Pharmacol Ther 1992 Nov;52(5):471-478."
],
"dapsone": [
"Microsomal codeine N-demethylation: Cosegregation with cytochrome P4503A4 activity. [ PMID 8818573 ] Caraco Y, Tateishi T, Guengerich FP, Wood AJJ. Metab Dispos 1996;24(7):761-764."
],
"dexamethasone": [
""
],
"dextromethorphan": [
"Dextromethorphan as an in vivo probe for the simultaneous determination of CYP2D6 and CYP3A activity. [ PMID 8861661 ] Ducharme J, Abdullah S, Wainer IW. Chromatogr B Biomed Appl 1996 Mar 29;678(1):113-28.",
"Characterization of dextromethorphan N-demethylation by human liver microsomes. Contribution of the cytochrome P450 3A (CYP3A) subfamily. [ PMID 8043020 ] Gorski JC, Jones DR, Wrighton SA, Hall SD. Biochem Pharmacol 1994 Jul 5;48(1):173-82."
],
"diazepam": [
"Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N-demethylation in the substrate-concentration-dependent manner. [ PMID 8148870 ] Yasumori T, Nagata K, Yang SK, Chen L-S, Murayama N, Yamazoe Y, Kato R. Pharmacogenetics 1993;3:291-301."
],
"docetaxel": [
"Effect of cytochrome P450 3A4 inhibition on the pharmacokinetics of docetaxel. [ PMID 15116057 ] Engels FK, Ten Tije AJ, Baker SD, Lee CK, Loos WJ, Vulto AG, Verweij J, Sparreboom A. Clin Pharmacol Ther. 2004 May;75(5):448-54."
],
"domperidone": [
"Characterization of human cytochrome P450 enzymes catalyzing domperidone N-dealkylation and hydroxylation in vitro. [ PMID 15327587 ] Ward BA, Morocho A, Kandil A, Galinsky RE, Flockhart DA, Desta Z. Br J Clin Pharmacol. 2004 Sep;58(3):277-87."
],
"diltiazem": [
"Role of CYP3A4 in human hepatic diltiazem N-demethylation: inhibition of CYP3A4 activity by oxidized diltiazem metabolites. [ PMID 9223567 ] Sutton D, Butler AM, Nadin L, Murray M. Pharmacol Exp Ther 1997 Jul;282(1):294-300."
],
"erythromycin": [
"Human cytochrome P450 3A4-catalyzed testosterone 6 beta-hydroxylation and erythromycin N-demethylation. Competition during catalysis. [ PMID 9107550 ] Wang RW, Newton DJ, Scheri TD, Lu AY. Metab Dispos 1997 Apr;25(4):502-507."
],
"estradiol": [
""
],
"felodipine": [
"Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. [ PMID 9153299 ] Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. Clin Invest 1997 May 15;99(10):2545-2553.",
"Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. [ PMID 8689808 ] Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD. Clin Pharmacol Ther 1996 Jul;60(1):25-33.",
"Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4. [ PMID 2061924 ] Guengerich FP, Brian WR, Iwasaki M, Sari MA, Baarnhielm C, Berntsson P. J Med Chem 1991 Jun;34(6):1838-1844."
],
"fentanyl": [
"Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. [ PMID 8886601 ] Feierman DE, Lasker JM. Drug Metab Dispos 1996;24(9):932-939."
],
"finasteride": [
"Identification of human cytochrome P450 isozymes responsible for the in vitro oxidative metabolism of finasteride. [ PMID 8654202 ] Huskey SW, Dean DC, Miller RR, Rasmusson GH, Chiu SH. Drug Metab Dispos 1995 Oct;23(10):1126-35 (Published erratum appears in Drug Metab Dispos 1996 Jun;24(6):695)"
],
"gestodene": [
""
],
"gleevec": [
""
],
"haloperidol": [
"In-vitro characterization of the cytochrome P450 isoenzymes involved in the back oxidation and N-dealkylation of reduced haloperidol. [ PMID 9825830 ] Pan LP, De Vriendt C, Belpaire FM. Pharmacogenetics 1998 Oct;8(5):383-9.",
"Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation. [ PMID 9681669 ] Kudo S, Odomi M. J Clin Pharmacol 1998 May;54(3):253-9.",
"Characterization of the cytochrome P450 isoenzymes involved in the in vitro N-dealkylation of haloperidol. [ PMID 9431831 ] Pan LP, Wijnant P, De Vriendt C, Rosseel MT, Belpaire FM. J Clin Pharmacol 1997 Dec;44(6):557-64."
],
"hydrocortisone": [
""
],
"indinavir": [
"Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. [ PMID 9616191 ] Koudriakova T, Iatsimirskaia E, Utkin I, Gangl E, Vouros P, Storozhuk E, Orza D, Marinina J, Gerber N. Drug Metab Dispos 1998 Jun;26(6):552-561."
],
"irinotecan": [
"Modulation of irinotecan metabolism by ketoconazole. [ PMID 12118026 ] Kehrer DF, Mathijssen RH, Verweij J, De Bruijn P, Sparreboom A. J Clin Oncol 2002 Jul 15;20(14):3122-9.",
"Metabolism of irinotecan (CPt-11) by CYP3A4 and CYP3a5 in humans. [ PMID 10815927 ] Santos A, Zanetta S, Cresteil T, Deroussent A, Pein F, Raymond E, Vernillet L, Risse ML, Boige V, Gouyette A, Vassal G. Clin Cancer Res. 2000 May;6(5):2012-20.",
"A new metabolite of irinotecan in which formation is mediated by human hepatic cytochrome P-450 3A4. [ PMID 11602529 ] Sai K, Kaniwa N, Ozawa S, Sawada JI. Drug Metab Dispos 2001 Nov;29(11):1505-13."
],
"lapatinib": [
""
],
"lercanidipine": [
""
],
"lidocaine": [
"Lidocaine metabolism in human liver microsomes by cytochrome P450 IIIA4. [ PMID 2582709 ] Bargetzi MJ, Aoyama T, Gonzalez FJ and Meyer UA. Clin Pharmacol Ther 1989;46(5):521-527"
],
"lovastatin": [
"Itraconazole drastically increases plasma concentrations of lovastatin and lovastatic acid. [ PMID 8689812 ] Neuvonen PJ, Jalava K-M. Clin Pharmacol Ther 1996;60(1):54-61."
],
"methandone": [
"The involvement of cytochrome P450 3A4 in the N-demethylation of L-alpha-acetylmethadol (LAAM), norLAAM, and methadone. [ PMID 9394023 ] Moody DE, Alburges ME, Parker RJ, Collins JM, Strong JM. Clin Pharmacol Ther 1996;60(1):54-61.",
"Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. [ PMID 8839037 ] Iribarne C, Berthou F, Baird S, Dreano Y, Picart D, Bail JP, Beaune P, Menez JF. Chem Res Toxicol 1996 Mar;9(2):365-373."
],
"midazolam": [
"Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. [ PMID 8185679 ] Gorski JC, Hall SD, Jones DR, VandenBranden M, Wrighton SA. Biochem Pharmacol 1994;47(9):1643-1653."
],
"nateglinide": [
""
],
"nelfinavir": [
""
],
"nifedipine": [
""
],
"nisoldipine": [
"Effect of grapefruit juice and naringen on nisoldipine pharmacokinetics. [ PMID 8275614 ] Bailey DG, Arnold MO, Strong A, Munoz C, Spence JD. Clin Pharmacol Ther 1993;54(6):589-594."
],
"nitrendipine": [
""
],
"odanestron (in part)": [
"Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. [ PMID 8591723 ] Dixon CM, Colthup PV, Serabjit-Singh CJ, Kerr BM, Boehlert CC, Park GR, Tarbit MH. Drug Metab Dispos 1995 Nov;23(11):1225-1230."
],
"oscarbazepine": [
"Spotlight on oxcarbazepine in epilepsy. [ PMID 14731060 ] Bang LM, Goa KL. CNS Drugs. 2004;18(1):57-61."
],
"pimozide": [
"Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. [ PMID 9580580 ] Desta Z, Kerbusch T, Soukhova N, Richard E, Ko JW, Flockhart DA. J Pharmacol Exp Ther 1998 May;285(2):428-37."
],
"not pravastatin": [
"Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. [ PMID 9542477 ] Neuvonen PJ, Kantola T, Kivisto KT. Clin Pharmacol Ther 1998 Mar;63(3):332-341.",
"Biotransformation of pravastatin sodium in humans. [ PMID 1680649 ] Everett DW, Chando TJ, Didonato GC, Singhvi SM, Pan HY, Weinstein SH. Drug Metab Dispos 1991 Jul;19(4):740-748."
],
"progesterone": [
""
],
"propranolol": [
"The influence of diltiazem versus cimetidine on propranolol metabolism. [ PMID 1487547 ] Tateishi T, Ohashi K, Fujimura A, Ebihara A. J. Clin. Pharm. 32:1099-1104, 1992."
],
"quetiapine": [
"Metabolic mechanism of quetiapine in vivo with clinical therapeutic dose. [ PMID 15834460 ] Li KY, Li X, Cheng ZN, Li HD. Methods Find Exp Clin Pharmacol. 2005 Mar;27(2):83-6."
],
"quinidine": [
"CO binding kinetics of human cytochrome P450 3A4. Specific interaction of substrates with kinetically distinguishable conformers. [ PMID 7890608 ] Koley AP, Buters JT, Robinson RC, Markowitz A, Friedman FK. J Biol Chem 1995 Mar 10;270(10):5014-5018."
],
"quinine": [
""
],
"risperidone": [
"Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. [ PMID 7690693 ] Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, Zylicz Z, Visscher HW, Jonkman JH. Clin Pharmacol Ther. 1993 Sep;54(3):257-68."
],
"ritonavir": [
"Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. [ PMID 9616191 ] Koudriakova T, Iatsimirskaia E, Utkin I, Gangl E, Vouros P, Storozhuk E, Orza D, Marinina J, Gerber N. Drug Metab Dispos 1998 Jun;26(6):552-561."
],
"not rosuvastatin": [
"Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects. [ PMID 12534645 ] Cooper KJ, Martin PD, Dane AL, Warwick MJ, Raza A, Schneck DW. Br J Clin Pharmacol. 2003 Jan;55(1):94-9."
],
"salmeterol": [
"The aliphatic oxidation of salmeterol to alpha-hydroxy salmeterol in human liver microsomes is catalyzed by cytochrome P450 3A. [ PMID 8723736 ] Manchee GR, Eddershaw PJ, Ranshaw LE, Herriott D, Park GR, Bayliss MK, Tarbit MH. Drug Metab Dispos 1996;24(5): 555-559."
],
"saquinavir": [
"Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4: potential contribution to high first-pass metabolism. [ PMID 9029057 ] Fitzsimmons ME, Collins JM. Drug Metab Dispos 1997 Feb;25(2):256-266.",
"Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations. [ PMID 9084959 ] Barry M, Gibbons S, Back D, Mulcahy F. Clin Pharmacokinet 1997 Mar;32(3):194-209."
],
"sildenafil": [
"The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers. [ PMID 11879258 ] Muirhead GJ, Faulkner S, Harness JA, Taubel J. Br J Clin Pharmacol 2002 Feb;53 Suppl 1:37S-43S."
],
"simvastatin": [
"In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. [ PMID 9321523 ] Prueksaritanont T, Gorham LM, Ma B, Liu L, Yu X, Zhao JJ, Slaughter DE, Arison BH, Vyas KP. Drug Metab Dispos 1997 Oct;25(10):1191-1199."
],
"sirolimus": [
""
],
"sorafenib": [
"Sorafenib: new drug. Second-line treatment of kidney cancer: better evaluated than sunitinib. [ PMID 17724834 ] [No authors listed] Prescrire Int. 2007 Aug;16(90):141-3.",
"Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. [ PMID 16133532 ] Lathia C, Lettieri J, Cihon F, Gallentine M, Radtke M, Sundaresan P. Cancer Chemother Pharmacol. 2006 May;57(5):685-92.",
"Prescribing Information"
],
"star fruit": [
""
],
"sunitinib": [
""
],
"tacrolimus": [
"Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. [ PMID 9246018 ] Floren LC, Bekersky I, Benet LZ, Mekki Q, Dressler D, Lee JW, Roberts JP, Hebert MF. Clin Pharmacol Ther 1997 Jul;62(1):41-49.",
"Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human liver microsomes. [ PMID 8866917 ] Christians U, Schmidt G, Bader A, Lampen A, Schottmann R, Linck A, Sewing KF. Br J Clin Pharmacol 1996 Mar;41(3):187-190.",
"Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. [ PMID 8689938 ] Lampen A, Christians U, Guengerich FP, Watkins PB, Kolars JC, Bader A, Gonschior AK, Dralle H, Hackbarth I, Sewing KF. Drug Metab Dispos 1995 Dec;23(12):1315-1324.",
"Metabolism of FK506, a potent immunosuppressive agent, by cytochrome P450 3A enzymes in rat, dog and human liver microsomes. [ PMID 7510480 ] Shiraga T, Matsuda H, Nagase K, Iwasaki K, Noda K, Yamazaki H, Shimada T, Funae Y. Biochem Pharmacol 1994 Feb 11;47(4):727-735.",
"Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. [ PMID 1385058 ] Sattler M, Guengerich FP, Yun CH, Christians U, Sewing KF. Drug Metab Dispos 1992 Sep;20(5):753-761.",
"In vitro metabolism of FK506 in rat, rabbit and human liver microsomes: identification of a major metabolite and of cytochrome P450 3A as the major enzyme responsible for its metabolism. [ PMID 1373595 ] Vincent SH, Karanam BV, Painter SK, Chiu SHL. Arch Biochem Biophys 192;294(2):454-460."
],
"tamoxifen": [
"Delineation of human cytochromes P450 involved in the metabolism of tamoxifen. Daniels, L., Blankson, E.A., Henderson, C.J., Harris, A.H., Wolf, C.R., Lennard, M.S., and Tucker, G.T. Br J Clin Pharmacol 33:153P, 1992."
],
"taxol": [
""
],
"telaprevir": [
""
],
"telithromycin": [
""
],
"terfenadine": [
"Oxidation of the antihistaminic drug terfenadine in human liver microsomes. Role of cytochrome P-450 3A(4) in -dealkylation and C-hydroxylation. [ PMID 1385058 ] Yun CH, Okerholm RA, Guengerich FP. Drug Metab Dispos 1993 May-Jun;21(3):403-9."
],
"testosterone": [
""
],
"torisel": [
""
],
"trazodone": [
""
],
"triazolam": [
"Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. [ PMID 8632299 ] von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, Shader RI. J Pharmacol Exp Ther 1996 Feb;276(2):370-379."
],
"verapamil": [
"Overlapping substrate specificities of cytochrome P450 3A and P-glycoprotein for a novel cysteine protease inhibitor. [ PMID 9531525 ] Zhang Y, Guo X, Lin ET, Benet LZ. Drug Metab Dispos 1998 Apr;26(4):360-6."
],
"vincristine": [
"Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL. [ PMID 8534764 ] Bohme A, Ganser A, Hoelzer D. Ann Hematol 1995 Dec;71(6):311-2.",
"Vincristine toxicity in five children with acute lymphoblastic leukemia. [ PMID 7623589 ] Murphy JA, Ross LM, Gibson BE. Lancet 1995 Aug 12;346(8972):443."
],
"zaleplon": [
""
],
"ziprasidone": [
""
],
"zolpidem": [
"Inhibitors Begin",
""
]
},
"inducers": {
"barbiturates": [
""
],
"carbamazepine": [
""
],
"efavirenz": [
""
],
"glucocorticoids": [
"Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. [ PMID 3654968 ] Watkins PB, WrightonSA, Schuetz EG, Molowa DT, Guzelian PS. J Clin Invest 1987;80:1029-1036."
],
"modafinil": [
"In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. [ PMID 10820139 ] Robertson P, DeCory HH, Madan A, Parkinson A. Drug Metab Dispos 2000 Jun;28(6):664-71.",
"Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers. [ PMID 11823757 ] Robertson P Jr, Hellriegel ET, Arora S, Nelson M. Clin Pharmacol Ther 2002 Jan;71(1):46-56."
],
"nevirapine": [
""
],
"oxcarbazepine": [
""
],
"phenobarbital": [
""
],
"phenytoin": [
""
],
"pioglitazone": [
""
],
"rifabutin": [
""
],
"rifampin": [
""
],
"st. john's wort": [
"Indinavir concentrations and St. John's wort. [ PMID 10683007 ] Stephen C. Piscitelli, Aaron H. Burstein, Doreen Chaltt, Raul M. Alfaro, Judith Falloon. The Lancet 2000 February 12;355(9203):548-549.",
"Acute heart transplant rejection due to St. John's wort. [ PMID 10683008 ] Ruschitzka F, Meier PJ, Turina M, Lüscher TF, Noll G. Lancet. 2000 February 12;355(9203):548-549."
]
},
"inhibitors": {
"amiodarone": [
""
],
"aprepitant": [
"Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. [ PMID 14973304 ] Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA. J Clin Pharmacol. 2004 Mar;44(3):215-23.",
"Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. [ PMID 12891225 ] Majumdar AK, McCrea JB, Panebianco DL, Hesney M, Dru J, Constanzer M, Goldberg MR, Murphy G, Gottesdiener KM, Lines CR, Petty KJ, Blum RA. Clin Pharmacol Ther. 2003 Aug;74(2):150-6.",
"Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting. [ PMID 15562136 ] Massaro AM, Lenz KL. Ann Pharmacother. 2005 Jan;39(1):77-85.",
"Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. [ PMID 15304427 ] Sanchez RI, Wang RW, Newton DJ, Bakhtiar R, Lu P, Chiu SH, Evans DC, Huskey SE. Drug Metab Dispos. 2004 Nov;32(11):1287-92.",
"Effects of the neurokinin1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. [ PMID 12844131 ] McCrea JB, Majumdar AK, Goldberg MR, Iwamoto M, Gargano C, Panebianco DL, Hesney M, Lines CR, Petty KJ, Deutsch PJ, Murphy MG, Gottesdiener KM, Goldwater DR, Blum RA. Clin Pharmacol Ther. 2003 Jul;74(1):17-24.",
"Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. [ PMID 14973304 ] Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA. J Clin Pharmacol. 2004 Mar;44(3):215-23."
],
"not azithromycin": [
""
],
"cimetidine": [
"Torsade de pointes during the concomitant use of terfenadine and cimetidine. [ PMID 8775544 ] Ng PW, Chan WK, Chan TY. Aust N Z J Med 1996 Feb;26(1):120-121.",
"The effect of cimetidine on cyclosporine A levels in liver transplant recipients: a preliminary report. [ PMID 1539561 ] Puff MR, Carey WD. Am J Gastroenterol 1992 Mar;87(3):287-291."
],
"ciprofloxacin": [
"Methadone, ciprofloxacin, and adverse drug reactions. [ PMID 11145498 ] Herrlin K, Segerdahl M, Gustafsson LL, Kalso E. Lancet 2000 Dec 16;356(9247):2069-70.",
"Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human. [ PMID 8894516 ] McLellan RA, Drobitch RK, Monshouwer M, Renton KW. Drug Metab Dispos 1996 Oct;24(10):1134-8."
],
"clarithromycin": [
"Oxidative metabolism of clarithromycin in the presence of human liver microsomes. Major role for the cytochrome P4503A (CYP3A) subfamily. [ PMID 9152603 ] Rodrigues AD, Roberts EM, Mulford DJ, Yao Y, Ouellet D. Metab Dispos 1997 May;25(5):623-630.",
"Effects of clarithromycin on cytochrome P450. Comparison with other macrolides. [ PMID 2527301 ] Tinel M, Descatoire V, Larrey D, Loeper J, Labbe G, Letteron P, Pessayre D. Pharmacol Exp Ther 1989;250(2):746-751.",
"Interaction between FK506 and clarithromycin in a renal transplant patient. [ PMID 753213 ] Wolter K, Wagner K, Philipp T, Fritschka E. Eur J Clin Pharmacol 1994;47:207-208.",
"Assessing the clinical significance of botanical supplementation on human cytochrome P450 3A activity: comparison of a milk thistle and black cohosh product to rifampin and clarithromycin. [ PMID 16432272 ] Gurley B, Hubbard MA, Williams DK, Thaden J, Tong Y, Gentry WB, Breen P, Carrier DJ, Cheboyina S. J Clin Pharmacol. 2006 Feb;46(2):201-13.",
"Dose-dependent inhibition of CYP3A activity by clarithromycin during Helicobacter pylori eradication therapy assessed by changes in plasma lansoprazole levels and partial cortisol clearance to 6beta-hydroxycortisol. [ PMID 12152002 ] Ushiama H, Echizen H, Nachi S, Ohnishi A. Clin Pharmacol Ther. 2002 Jul;72(1):33-43."
],
"diltiazem": [
"Diltiazem inhibition of cytochrome P-450 3A activity is due to metabolite intermediate complex formation. [ PMID 8968170 ] Jones DR, Gorski JC, Hamman MA, Mayhew BS, Rider S, Hall SD. Pharmacol Exp Ther. 1999 Sep;290(3):1116-25.",
"Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting. [ PMID 15801939 ] Ahonen J, Olkkola KT, Salmenperä M, Hynynen M, Neuvonen PJ. Anesthesiology. 1996 Dec;85(6):1246-52.",
"Diltiazem inhibits human intestinal cytochrome P450 3A (CYP3A) activity in vivo without altering the expression of intestinal mRNA or protein. [ PMID 15801939 ] Pinto AG, Horlander J, Chalasani N, Hamman M, Asghar A, Kolwankar D, Hall SD. Br J Clin Pharmacol. 2005 Apr;59(4):440-6.",
"The interaction of diltiazem with simvastatin. [ PMID 8968170 ] Mousa O, Brater DC, Sunblad KJ, Hall SD. Clin Pharmacol Ther. 2000 Mar;67(3):267-74."
],
"delaviridine": [
""
],
"diethyl-dithiocarbamate": [
"Biotransformation of chloroxazone by hepatic microsomes from humans and ten other mammalian species. [ PMID 8968170 ] Mousa O, Brater DC, Sunblad KJ, Hall SD. Court MH, Von Moltke LL, Shader RI, Greenblatt DJ. Biopharm Drug Dispos 18(3):213-226; 1997."
],
"erythromycin": [
"Effect of the treatment period with erythromycin on cytochrome P450 3A activity in humans. [ PMID 17585116 ] Okudaira T, Kotegawa T, Imai H, Tsutsumi K, Nakano S, Ohashi K. Court MH, Von Moltke LL, Shader RI, Greenblatt DJ. J Clin Pharmacol. 2007 Jul;47(7):871-6."
],
"fluconazole": [
"Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants: relation to pharmacokinetic interactions in vivo. [ PMID 8690825 ] von Moltke LL, Greenblatt DJ, Duan SX, Harmatz JS, Wright CE, Shader RI. Court MH, Von Moltke LL, Shader RI, Greenblatt DJ. J Clin Psychopharmacol. 1996 Apr;16(2):104-12.",
"Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression. [ PMID 9929500 ] Gibbs MA, Thummel KE, Shen DD, Kunze KL. Drug Metab Dispos. 1999 Feb;27(2):180-7.",
"Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism. [ PMID 8730978 ] Varhe A, Olkkola KT, Neuvonen PJ. Br J Clin Pharmacol. 1996 Apr;41(4):319-23."
],
"fluvoxamine": [
"Selective serotonin reuptake inhibitors and theophylline metabolism in human liver microsomes: potent inhibition by fluvoxamine. [ PMID 8690825 ] Rasmussen BB, Mäenpää J, Pelkonen O, Loft S, Poulsen HE, Lykkesfeldt J, Brøsen K. Br J Clin Pharmacol 1995;39:151-160."
],
"gestodene": [
""
],
"grapefruit juice": [
"Interaction between grapefruit juice and diazepam in humans. [ PMID 9625273 ] Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A. J Drug Metab Pharmacokinet 1998 Jan;23(1):55-59.",
"Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. [ PMID 9153299 ] Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. Clin Invest 1997 May 15;99(10):2545-2553.",
"Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. [ PMID 16513448 ] Culm-Merdek KE, von Moltke LL, Gan L, Horan KA, Reynolds R, Harmatz JS, Court MH, Greenblatt DJ. Clin Pharmacol Ther. 2006 Mar;79(3):243-54.",
"Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice. [ PMID 12953340 ] Veronese ML, Gillen LP, Burke JP, Dorval EP, Hauck WW, Pequignot E, Waldman SA, Greenberg HE. J Clin Pharmacol. 2003 Aug;43(8):831-9.",
"Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. [ PMID 9153299 ] Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. J Clin Invest. 1997 May 15;99(10):2545-53."
],
"imatinib": [
"Severe pustular eruption associated with imatinib and voriconazole in a patient with chronic myeloid leukemia. [ PMID 9616191 ] Gambillara E, Laffitte E, Widmer N, Decosterd LA, Duchosal MA, Kovacsovics T, Panizzon RG. Dermatology. 2005;211(4):363-5."
],
"indinavir": [
"Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, Daily JP, Harmatz JS, Shader RI. J Clin Pharmacol. 1998 Feb;38(2):106-11.",
"Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor. [ PMID 8820421 ] Chiba M, Hensleigh M, Nishime JA, Balani SK, Lin JH. Drug Metab Dispos 1996 Mar;24(3):307-14."
],
"interleukin": [
"In vivo effects of interleukin-10 on human cytochrome P450 activity. [ PMID 10668851 ] Gorski JC, Hall SD, Becker P, Affrime MB, Cutler DL, Haehner-Daniels B. Clin Pharmacol Ther 2000 Jan;67(1):32-43."
],
"itraconazole": [
"Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants: relation to pharmacokinetic interactions in vivo. [ PMID 8690825 ] von Moltke LL, Greenblatt DJ, Duan SX, Harmatz JS, Wright CE, Shader RI. J Clin Psychopharmacol. 1996 Apr;16(2):104-12."
],
"ketoconazole": [
"Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants: relation to pharmacokinetic interactions in vivo. [ PMID 8690825 ] von Moltke LL, Greenblatt DJ, Duan SX, Harmatz JS, Wright CE, Shader RI. J Clin Psychopharmacol. 1996 Apr;16(2):104-12.",
"Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. [ PMID 1371482 ] Maurice M, Pichard L, Daujat M. Fabre I, Joyeux H, Domergue J, Maurel P. FASEB J. 1992;6:752-758.",
"Ketoconazole, a cytochrome P450 3A4 inhibitor, markedly increases concentrations of levo-acetyl-alpha-methadol in opioid-naive individuals. [ PMID 15289792 ] Moody DE, Walsh SL, Rollins DE, Neff JA, Huang W. Clin Pharmacol Ther. 2004 Aug;76(2):154-66.",
"Influence of ketoconazole on the fecal and urinary disposition of docetaxel. [ PMID 17256132 ] Engels FK, Loos WJ, Mathot RA, van Schaik RH, Verweij J. Cancer Chemother Pharmacol. 2007 Sep;60(4):569-79."
],
"mibefradil": [
"Mibefradil is a P-glycoprotein substrate and a potent inhibitor of both P-glycoprotein and CYP3A in vitro. [ PMID 10901697 ] Wandel C, Kim RB, Guengerich FP, Wood AJ. Drug Metab Dispos 2000 Aug;28(8):895-8."
],
"mifepristone": [
"Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone. [ PMID 9918590 ] He K, Woolf TF, Hollenberg PF. J Pharmacol Exp Ther 1999 Feb;288(2):791-7."
],
"nefazodone": [
"Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. [ PMID 8632299 ] von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE, Shader RI. J Pharmacol Exp Ther 1996 Feb;276(2):370-379.",
"Interactions between cyclosporine and newer antidepressant medications. [ PMID 9469504 ] Vella JP, Sayegh MH. J Kidney Dis 1998 Feb;31(2):320-323.",
"Nefazodone relief of alprazolam interdose dysphoria: a potential therapeutic benefit of 3A3/4 inhibition. [ PMID 8666573 ] Ketter TA, Callahan AM, Post R. J Clin Psychiatry 1996 Jul;57(7):307.",
"Nefazodone, meta-chlorophenylpiperazine, and their metabolites in vitro: cytochromes mediating transformation, and P450-3A4 inhibitory actions. [ PMID 10445380 ] von Moltke LL, Greenblatt DJ, Granda BW, Grassi JM, Schmider J, Harmatz JS, Shader RI. Psychopharmacology (Berl). 1999 Jul;145(1):113-22.",
"Coadministration of nefazodone and benzodiazepines: II. A pharmacokinetic interaction study with triazolam. [ PMID 8830062 ] Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS. J Clin Psychopharmacol. 1995 Oct;15(5):320-6."
],
"nelfinavir": [
"Severe pustular eruption associated with imatinib and voriconazole in a patient with chronic myeloid leukemia. [ PMID 9616191 ] Gambillara E, Laffitte E, Widmer N, Decosterd LA, Duchosal MA, Kovacsovics T, Panizzon RG. Dermatology. 2005;211(4):363-5.",
"Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. [ PMID 9660842 ] Lillibridge JH, Liang BH, Kerr BM, Webber S, Quart B, Shetty BV, Lee CA. Drug Metab Dispos. 1998 Jul;26(7):609-16."
],
"norfloxacin": [
"Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism in rat and human. [ PMID 8894516 ] McLellan RA, Drobitch RK, Monshouwer M, Renton KW. Drug Metab Dispos 1996 Oct;24(10):1134-8."
],
"norfluoxetine": [
"Drug Therapy: Fluoxetine. [ PMID 7935707 ] Brosen K. N Eng J Med 1994;331(20):1354-1361."
],
"ritonavir": [
"Protease inhibitors as inhibitors of human cytochromes P450: high risk associated with ritonavir. [ PMID 9549640 ] von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Duan SX, Fogelman SM, Daily JP, Harmatz JS, Shader RI. J Clin Pharmacol 1998 Feb;38(2):106-111.",
"Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. [ PMID 9812178 ] Hsu A, Granneman GR, Bertz RJ. Clin Pharmacokinet. 1998 Oct;35(4):275-91.",
"Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. [ PMID 10668858 ] Dresser GK, Spence JD, Bailey DG. Clin Pharmacokinet. 2000 Jan;38(1):41-57.",
"Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. [ PMID 16513448 ] Culm-Merdek KE, von Moltke LL, Gan L, Horan KA, Reynolds R, Harmatz JS, Court MH, Greenblatt DJ. Clin Pharmacol Ther. 2006 Mar;79(3):243-54."
],
"saquinavir": [
""
],
"starfruit": [
""
],
"telithromycin": [
"Telithromycin, but not montelukast, increases the plasma concentrations and effects of the cytochrome P450 3A4 and 2C8 substrate repaglinide. [ PMID 16513447 ] Kajosaari LI, Niemi M, Backman JT, Neuvonen PJ. Clin Pharmacol Ther. 2006 Mar;79(3):231-42.",
"General Framework for the Quantitative Prediction of CYP3A4-Mediated Oral Drug Interactions Based on the AUC Increase by Coadministration of Standard Drugs. [ PMID 17655375 ] Ohno Y, Hisaka A, Suzuki H. Clin Pharmacokinet. 2007;46(8):681-96.",
"Verapamil toxicity resulting from a probable interaction with telithromycin. [ PMID 15598962 ] Reed M, Wall GC, Shah NP, Heun JM, Hicklin GA. Ann Pharmacother. 2005 Feb;39(2):357-60.",
"Pharmacokinetics of telithromycin: application to dosing in the treatment of community-acquired respiratory tract infections. [ PMID 16238904 ] Ciervo CA, Shi J. Curr Med Res Opin. 2005 Oct;21(10):1641-50."
],
"verapamil": [
"Prediction of cytochrome P450 3A inhibition by verapamil enantiomers and their metabolites. [ PMID 14744949 ] Wang YH, Jones DR, Hall SD. Drug Metab Dispos. 2004 Feb;32(2):259-66.",
"The effect of short- and long-term administration of verapamil on the disposition of cytochrome P450 3A and P-glycoprotein substrates. [ PMID 16513446 ] Lemma GL, Wang Z, Hamman MA, Zaheer NA, Gorski JC, Hall SD. Clin Pharmacol Ther. 2006 Mar;79(3):218-30.",
"Comparative studies to determine the selective inhibitors for P-glycoprotein and cytochrome P4503A4. [ PMID 11741214 ] Achira M, Suzuki H, Ito K, Sugiyanma Y. AAPS PharmSci 1999;1(4):E18.",
"Erythromycin and verapmil considerably increase serum simvastatin and simvastatin acid concentrations. [ PMID 9728898 ] Kantola T, Kivisto KT, Neuvonen PJ. Clin Pharmacol Ther 1998 Aug;64(2):177-82.",
"Metabolism of the immunosuppressant tacrolimus in the small intestine: Cytochrome P450, drug interactions, and interindividual variability. [ PMID 8689938 ] Lampen A, Christians U, Guengerich FP, Watkins PB, Kolars JC, Bader A, Gonschior AK, Dralle H, Hackbarth I, Sewing KF. Drug Metab Dispos 1995 Dec;23(12):1315-24.",
"Inhibitory effects of verapamil and diltiazem on simvastatin metabolism in human liver microsomes. [ PMID 11422004 ] Yeo KR and Yeo WW. Br J Clin Pharmacol. 2001 May;51(5):461-70."
],
"voriconazole": [
"Drug-drug interaction of antifungal drugs. [ PMID 16205037 ] Niwa T, Shiraga T, Takagi A. Yakugaku Zasshi. 2005 Oct;125(10):795-805."
]
}
},
"2c8": {
"substrates": {
"amodiaquine": [
"Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. [ PMID 11805197 ] Li XQ, Bjorkman A, Andersson TB, Ridderstrom M, Masimirembwa CM. J Pharmacol Exp Ther. 2002 Feb;300(2):399-407."
],
"cerivastatin": [
"Clinical pharmacokinetics of cerivastatin. [ PMID 10976657 ] Mück W. Clin Pharmacokinet. 2000 Aug;39(2):99-116.",
"Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. [ PMID 12433802 ] Wang JS, Neuvonen M, Wen X, Backman JT, Neuvonen PJ. Drug Metab Dispos. 2002 Dec;30(12):1352-6."
],
"paclitaxel": [
"Paclitaxel metabolism in rat and human liver microsomes is inhibited by phenolic antioxidants. [ PMID 12920504 ] Vaclavikova R, Horsky S, Simek P, Gut I. Naunyn Schmiedebergs Arch Pharmacol. 2003 Sep;368(3):200-9."
],
"repaglinide": [
"CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. [ PMID 12919179 ] Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT. Br J Clin Pharmacol. 2003 Sep;56(3):305-14.",
"Polymorphism in CYP2C8 is associated with reduced plasma concentrations of repaglinide. [ PMID 14534525 ] Niemi M, Leathart JB, Neuvonen M, Backman JT, Daly AK, Neuvonen PJ. Clin Pharmacol Ther. 2003 Oct;74(4):380-7."
],
"sorafenib": [
"Prescribing Information"
],
"torsemide": [
"The xenobiotic inhibitor profile of cytochrome P4502C8. [ PMID 11136296 ] Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO. Br J Clin Pharmacol. 2000 Dec;50(6):573-80."
]
},
"inducers": {},
"inhibitors": {
"gemfibrozil": [
"Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. [ PMID 12433802 ] Wang JS, Neuvonen M, Wen X, Backman JT, Neuvonen PJ. Drug Metab Dispos. 2002 Dec;30(12):1352-6.",
"Gemfibrozil greatly increases plasma concentrations of cerivastatin. [ PMID 12496749 ] Backman JT, Kyrklund C, Neuvonen M, Neuvonen PJ. Clin Pharmacol Ther. 2002 Dec;72(6):685-91.",
"Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. [ PMID 12898007 ] Niemi M, Backman JT, Granfors M, Laitila J, Neuvonen M, Neuvonen PJ. Diabetologia. 2003 Oct;46(10):1319-23."
],
"glitazones (thiazolidinediones)": [
"Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. [ PMID 12642470 ] Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, Gilbert D, LeCluyse EL, Sinz MW. Drug Metab Dispos. 2003 Apr;31(4):439-46."
],
"montelukast": [
"Selective inhibition of human cytochrome P4502C8 by montelukast. [ PMID 15608135 ] Walsky RL, Obach RS, Gaman EA, Gleeson JP, Proctor WR. Drug Metab Dispos. 2005 Mar;33(3):413-8."
],
"quercetin": [
"Human cytochrome P450s involved in the metabolism of 9-cis- and 13-cis-retinoic acids. [ PMID 11911845 ] Marill J, Capron CC, Idres N, Chabot GG. Biochem Pharmacol. 2002 Mar 1;63(5):933-43."
],
"trimethoprim": [
"Trimethoprim and sulfamethoxazole are selective inhibitors of CYP2C8 and CYP2C9, respectively. [ PMID 12019187 ] Wen X, Wang JS, Backman JT, Laitila J, Neuvonen PJ. Drug Metab Dispos. 2002 Jun;30(6):631-5.",
"Effects of trimethoprim and rifampin on the pharmacokinetics of the cytochrome P450 2C8 substrate rosiglitazone. [ PMID 15371985 ] Niemi M, Backman JT, Neuvonen PJ.. Clin Pharmacol Ther. 2004 Sep;76(3):239-49.",
"The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects. [ PMID 15606443 ] Hruska MW, Amico JA, Langaee TY, Ferrell RE, Fitzgerald SM, Frye RF. Br J Clin Pharmacol. 2005 Jan;59(1):70-9.",
"The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects. [ PMID 15025742 ] Niemi M, Kajosaari LI, Neuvonen M, Backman JT, Neuvonen PJ. Br J Clin Pharmacol. 2004 Apr;57(4):441-7."
]
}
},
"1a2": {
"substrates": {
"amitriptyline": [
"Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. [ PMID 1905641 ] Bertschy G, Vandel S, Vandel B, Allers G, Volmat R. Eur J Clin Pharmacol 1991;40(1):119-120. [Letter]"
],
"caffeine": [
"Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans. [ PMID 8738764 ] Rasmussen BB, Brosen K. Ther Drug Monit 1996 Jun;18(3):254-262.",
"Assays for CYP1A2 by testing in vivo metabolism of caffeine in humans. [ PMID 8791769 ] Tang BK, Kalow W. Methods Enzymol 1996;272:124-131."
],
"clomipramine": [
"Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. [ PMID 1905641 ] Bertschy G, Vandel S, Vandel B, Allers G, Volmat R. Eur J Clin Pharmacol 1991;40(1):119-120. [Letter]"
],
"clozapine": [
"Metabolism and bioactivation of clozapine by human liver in vitro. [ PMID 7891353 ] Pirmohamed M, Williams D, Madden S, Templeton E, Park BK. J Pharmacol Exp Ther 272(3):984-990, 1995.",
"Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. [ PMID 7893591 ] Bertilsson L, Carrillo JA, Dahl ML, Llerena A, Alm C, Bondesson U, Lindström L, Rodriguez de la Rubia I, Ramos S, Benitez J. Br J Clin Pharmacol 38:471-473, 1994."
],
"cyclobenzaprine": [
"Identification of Human Liver Cytochrome P450 Isoforms involved in the in vitro metabolism of cyclobenzaprine. [ PMID 8818577 ] Wang RW, Liu L, Cheng H. Drug Metab Dispos 1996;24(7):786-791."
],
"fluvoxamine": [
"Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. [ PMID 8823236 ] Carillo JA, Dahl ML, Svennson JO, Alm C, Rodriguez I, Bertillson L. Clin Pharmacol Ther 1996;60:183-190."
],
"estradiol": [
"Differences in the cytochrome P-450 isoenzymes involved in the 2-hydroxylation of oestradiol and 17alpha-ethinyloestradiol. [ PMID 2327982",
"] Ball SE, Forrester LM, Wolf CR, Back DJ. Biochem J 267:221-226, 1990."
],
"haloperidol": [
"Coadministration of fluvoxamine increases serum concentrations of haloperidol. [ PMID 7806690 ] Daniel DG, Randolph C, Jaskiw G, Handel S, Williams T, Abi-Dargham A, Shoaf S, Egan M, Elkashef A, Liboff S, Linnoila M. J Clin Psychopharmacol 14:340-343, 1994."
],
"imipramine": [
"Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. [ PMID 9190854 ] Koyama E, Chiba K, Tani M, Ishizaki T J Pharmacol Exp Ther 1997 Jun;281(3):1199-1210",
"Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. [ PMID 8502233 ] Lemoine A, Gautier JC, Azoulay D, Kiffel L, Belloc C, Guengerich FP, Maurel P, Beaune P, Leroux JP Mol Pharmacol 1993 May;43(5):827-832"
],
"mexiletine": [
"CYP1A2 is the major enzyme involved in the metabolism of mexilitene in man. [ <a href=\"\" >PMID</a> ]<br />\nAbolfathi Z, Pakdel H, Beaune P, Turgeon J<br />\nClin Pharmacol Ther 1995;57(2):215 Abst.<br /><br />",
"Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic agent mexiletine. [ PMID 12519691",
"] Labbé L, Abolfathi Z, Lessard E, Pakdel H, Beaune P, Turgeon J. Xenobiotica. 2003 Jan;33(1):13-25.",
"Inhibition of human liver cytochrome P-450 1A2 by the class IB antiarrhythmics mexiletine, lidocaine, and tocainide. [ PMID 10215663 ] Wei X, Dai R, Zhai S, Thummel KE, Friedman FK, Vestal RE. J Pharmacol Exp Ther. 1999 May;289(2):853-8."
],
"naproxen": [
"Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. [ PMID 8866821 ] Miners JO, Coulter S, Tukey RH, Veronese ME, Birkett DJ Biochem Pharmacol 1996 Apr 26;51(8):1003-1008"
],
"olanzapine": [
"Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia. [ PMID 15545309 ] Chiu CC, Lane HY, Huang MC, Liu HC, Jann MW, Hon YY, Chang WH, Lu ML. J Clin Pharmacol. 2004 Dec;44(12):1385-90."
],
"ondansetron (in part)": [
"Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. [ PMID 8591723 ] Dixon CM, Colthup PV, Serabjit-Singh CJ, Kerr BM, Boehlert CC, Park GR, Tarbit MH Drug Metab Dispos 1995 Nov;23(11):1225-1230"
],
"phenacetin": [
"Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. [ PMID 8474022 ] Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO. J Pharmacol Exp Ther 1993 Apr;265(1):401-407.",
"Acetaminophen bioactivation by human cytochrome P450 enzymes and animal microsomes. [ PMID 19219744 ] Laine JE, Auriola S, Pasanen M, Juvonen RO. Xenobiotica. 2009 Jan;39(1):11-21."
],
"propranolol": [
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"Fluvoxamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. [ PMID 3096686 ] Benfield, P and Ward A Drugs 1986;32:313-334 [Fluvoxamine is a potent inhibitor of propranolol metabolism in vivo.]"
],
"riluzole": [
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],
"ropivacaine": [
"Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. [ PMID 9834040 ] Arlander E, Ekstrom G, Alm C, Carrillo JA, Bielenstein M, Bottiger Y, Bertilsson L, Gustafsson LL Clin Pharmacol Ther 1998 Nov;64(5):484-91"
],
"tacrine": [
"Determination of human hepatic cytochrome P450 1A2 activity in vitro: use of tacrine as an isozyme-specific probe. [ PMID 8565783 ] Spaldin V, Madden S, Adams DA, Edwards RJ, Davies DS, Park BK Drug Metab Dispos 1995;23(9):929-934"
],
"theophylline": [
"Metabolism of theophylline by cDNA-expressed human cytochromes P450. [ PMID 7619675 ] Ha HR, Chen J, Freiburghaus AU, Follath F Br J Clin Pharmacol 1995;39:321-326"
],
"tizanidine": [
"Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. [ PMID 15592331 ] Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Clin Pharmacol Ther. 2004 Dec;76(6):598-606",
"Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction. [ PMID 15060511 ] Granfors MT, Backman JT, Neuvonen M, Ahonen J, Neuvonen PJ. Clin Pharmacol Ther. 2004 Apr;75(4):331-41"
],
"verapamil": [
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"warfarin": [
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],
"zileuton": [
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],
"zolmitriptan": [
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]
},
"inducers": {
"broccoli": [
"Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers. [ PMID 17266520 ] Hakooz N, Hamdan I. Curr Drug Metab. 2007 Jan;8(1):9-15."
],
"brussel sprouts": [
"3,3-Diindolylmethane induces CYP1A2 in cultured precision-cut human liver slices. [ PMID 9741959 ] Lake BG, Tredger JM, Renwick AB, Barton PT, Price RJ. Xenobiotica. 1998 Aug;28(8):803-11."
],
"chargrilled meat": [
"Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers. [ PMID 10381914",
"] Fontana RJ, Lown KS, Paine MF, Fortlage L, Santella RM, Felton JS, Knize MG, Greenberg A, Watkins PB Gastroenterology 1999 Jul;117(1):89-98"
],
"insulin": [
"Hyperinsulinemia causes a preferential increase in hepatic P4501A2 activity. [ PMID 1562279 ] Barnett CR, Wilson J, Wolf CR, Flatt PR, Ioannides C Biochem Pharmacol 1992;43(6):1255-61"
],
"methylcholanthrene": [
"3-Methylcholanthrene and pyridine effects on CYP1A1 and CYP1A2 expression in rat renal tissue. [ PMID 7493548 ] H Kim, S Reddy, RF Novak Drug Metab Dispos. 1995 Aug;23(8):818-24.",
"Induction of CYP1A1, but not CYP1A2, in adrenals of 3, 3'-methylcholanthrene-treated guinea pigs. [ PMID 9637727] Black VH, Wang AF, Henry M, Shaw PM. Arch Biochem Biophys. 1998 Jun 15;354(2):197-205."
],
"modafinil": [
"In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. [ PMID 10820139 ] Robertson P, DeCory HH, Madan A, Parkinson A. Drug Metab Dispos 2000 Jun;28(6):664-71"
],
"nafcillin": [
"Interaction between warfarin and nafcillin: case report and review of the literature. [ PMID 10820139 ] Kim KY, Frey RJ, Epplen K, Foruhari F. Pharmacotherapy. 2007 Oct;27(10):1467-70."
],
"beta-naphthoflavone": [
"Involvement of the CYP1A Subfamily in Stereoselective Metabolism of Carvedilol in beta-Naphthoflavone-Treated Caco-2 Cells. [ PMID 19252307 ] Ishida K, Taguchi M, Akao T, Hashimoto Y. Biol Pharm Bull. 2009 Mar;32(3):513-6."
],
"omeprazole": [
"Increase of cytochrome P450IA2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. [ PMID 1505152 ] Rost KL, Brösicke H, Brockmöller J, Scheffler M, Helge H, Roots I. Clin Pharmacol Ther. 1992 Aug;52(2):170-80."
]
},
"inhibitors": {
"amiodarone": [
"Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed by human CYP1A2. [ PMID 9578183 ] Kobayashi K, Nakajima M, Chiba K, Yamamoto T, Tani M, Ishizaki T, Kuroiwa Y. Br J Clin Pharmacol 1998 Apr;45(4):361-368."
],
"cimetidine": [
"The effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6. [ PMID 16680870 ] Madeira M, Levine M, Chang TK, Mirfazaelian A, Bellward GD. Drug Metab Dispos. 2004 Apr;32(4):460-7.",
"Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. [ PMID 10223772 ] Martínez C, Albet C, Agúndez JA, Herrero E, Carrillo JA, Márquez M, Benítez J, Ortiz JA. Clin Pharmacol Ther. 1999 Apr;65(4):369-76.",
"Imipramine-cimetidine interaction: impairment of clearance and enhanced absolute bioavailability. [ PMID 6726654 ] Abernethy DR, Greenblatt DJ, Shader RI. J Pharmacol Exp Ther. 1984 Jun;229(3):702-5."
],
"ciprofloxacin": [
"Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. [ PMID 15592331 ] Granfors MT, Backman JT, Neuvonen M, Neuvonen PJ. Clin Pharmacol Ther. 2004 Dec;76(6):598-606."
],
"fluoroquinolones": [
"The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects. [ PMID 7619673 ] Batty K, Davis TME, Ilett KF, Dusci LJ, Langton SR. Br J Clin Pharmacol 1995;39(3):305-311."
],
"fluvoxamine": [
"Fluvoxamine is a potent inhibitor of cytochrome P4501A2. [ PMID 8466541 ] Brosen K, Skjelbo E, Rasmussen BB, Poulsen HE, Loft S. Biochem Pharmacol 1993 Mar 24;45(6):1211-1214.",
"Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2. [ PMID 9205822 ] Ball SE, Ahern D, Scatina J, Kao J. Br J Clin Pharmacol. 1997 Jun;43(6):619-26.",
"Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia. [ PMID 15545309 ] Chiu CC, Lane HY, Huang MC, Liu HC, Jann MW, Hon YY, Chang WH, Lu ML. J Clin Pharmacol. 2004 Dec;44(12):1385-90.",
"Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function. [ PMID 14749694 ] Orlando R, Piccoli P, De Martin S, Padrini R, Floreani M, Palatini P. Clin Pharmacol Ther. 2004 Jan;75(1):80-8.",
"Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2. [ PMID 11719727 ] Yao C, Kunze KL, Kharasch ED, Wang Y, Trager WF, Ragueneau I, Levy RH. Clin Pharmacol Ther. 2001 Nov;70(5):415-24.",
"Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. [ PMID 11240973 ] Kusumoto M, Ueno K, Oda A, Takeda K, Mashimo K, Takaya K, Fujimura Y, Nishihori T, Tanaka K. Clin Pharmacol Ther. 2001 Mar;69(3):104-7.",
"Fluvoxamine is a potent inhibitor of tacrine metabolism in vivo. [ PMID 10456487 ] Larsen JT, Hansen LL, Spigset O, Brøsen K. Eur J Clin Pharmacol. 1999 Jul;55(5):375-82.",
"Influence of the CYP1A2 inhibitor fluvoxamine on tacrine pharmacokinetics in humans. [ PMID 9209244 ] Becquemont L, Ragueneau I, Le Bot MA, Riche C, Funck-Brentano C, Jaillon P. Clin Pharmacol Ther. 1997 Jun;61(6):619-27."
],
"furafylline": [
"Furafylline is a potent and selective inhibitor of P4501A2 in man. [ PMID 2378786 ] Sesardic D, Boobis AR, Murray BP, Murray S, Segura J, de la Torre R, Davies DS. Br J Clin Pharmacol 1990;29:651-663"
],
"interferon": [
"Regulation of hepatic cytochrome P-450 during infectious disease. [ PMID 1695539 ] Renton KW, Knickle LC Can J Physiol Pharmacol 1990 Jun;68(6):777-781"
],
"methoxsalen": [
"Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. [ PMID 8819299 ] Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, Tsutsui M. Xenobiotica. 1996 Jul;26(7):681-93."
],
"mibefradil": [
"Metabolism of the calcium antagonist, mibefradil (POSICOR,Ro40-5967). Part III. Comparative pharmacokinetics of mibefradil and its major metabolites in rat, marmoset, cynomolgus monkey and man. [ PMID 9211656 ] Wiltshire HR, Sutton BM, Heeps G, Betty AM, Angus DW, Harris SR, Worth E, Welker HA Xenobiotica 1997 Jun;27(6):557-571"
]
}
},
"2d6": {
"substrates": {
"alprenolol": [
"Polymorphic drug oxidation in humans. [ PMID 6714436 ] Eichelbaum M. Fed Proc 1984 May 15;43(8):2298-2302.",
"Competitive inhibition of sparteine oxidation in human liver by beta-adrenoceptor antagonists and other cardiovascular drugs. [ PMID 6141510 ] Otton SV, Inaba T, Kalow W. Life Sci 1984 Jan 2;34(1):73-80."
],
"amitriptyline": [
"Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. [ PMID 3956053 ] Mellstrom B, Sawe J, Bertilsson L, Sjoqvist F. Clin Pharmacol Ther. 1986 Apr; 39(4): 369-371.",
"Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. [ PMID 3571939 ] Baumann P, Jonzier-Perey M, Koeb L, Kupfer A, Tinguely D, Schopf J. Int Clin Psychopharmacol. 1986 Apr; 1(2): 102-112."
],
"amphetamine": [
"The metabolic fate of amphetamine in man and other species. [ PMID 4985156 ] Dring LG, Smith RL, Williams TR. Biochem J 1970;425-435.",
"Introduction: human genetic variations in oxidative drug metabolism. Smith RL. Xenobiotica 1986;16:361-365."
],
"aripiprazole": [
"Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. [ PMID 15257633 ] Swainston Harrison T, Perry CM. Drugs. 2004;64(15):1715-36."
],
"atomoxetine": [
"Identification of the human cytochromes P450 responsible for atomoxetine metabolism. [ PMID 11854152 ] Ring BJ, Gillespie JS, Eckstein JA, Wrighton SA. Drug Metab Dispos. 2002 Mar;30(3):319-23."
],
"bufuralol": [
"Genetic polymorphism in drug oxidation: in vitro studies of human debrisoquine 4-hydroxylase and bufuralol 1'-hydroxylase activities. [ PMID 3966916 ] Boobis AR, Murray S, Hampden CE, Davies DS. Biochem Pharmacol 1985 Jan 1;34(1):65-71.",
"Characterization of a common genetic defect of cytochrome P-450 function (debrisoquine-sparteine type polymorphism)--increased Michaelis is Constant (Km) and loss of stereoselectivity of bufuralol 1'-hydroxylation in poor metabolizers. [ PMID 6508804 ] Dayer P, Gasser R, Gut J, Kronbach T, Robertz GM, Eichelbaum M, Meyer UA. Biochem Biophys Res Commun 1984 Nov 30;125(1):374-380.",
"Debrisoquine-type polymorphism of drug oxidation: purification from human liver of a cytochrome P450 isozyme with high activity for bufuralol hydroxylation. [ PMID 6146537 ] Gut J, Gasser R, Dayer P, Kronbach T, Catin T, Meyer UA. FEBS Lett 1984 Aug 6;173(2):287-290.",
"Enzymatic basis of the debrisoquine/sparteine-type genetic polymorphism of drug oxidation. Characterization of bufuralol 1'-hydroxylation in liver microsomes of in vivo phenotyped carriers of the genetic deficiency. [ PMID 3689440 ] Dayer P, Kronbach T, Eichelbaum M, Meyer UA. Biochem Pharmacol 1987 Dec 1;36(23):4145-4152."
],
"carvedilol": [
""
],
"chlorpheniramine": [
""
],
"chlorpromazine": [
""
],
"clomipramine": [
"Pharmacogenetics of antidepressants: clinical aspects. [ PMID 9265947 ] Bertilsson L, Dahl ML, Tybring G. Acta Psychiatr Scand Suppl 1997;391:14-21."
],
"clonidine": [
"CYP2D6 mediates 4-hydroxylation of clonidine in vitro: implication for pregnancy-induced changes in clonidine clearance. [ PMID 20570945 ] Claessens AJ, Risler LJ, Eyal S, Shen DD, Easterling TR, Hebert MF. Drug Metab Dispos. 2010 Sep;38(9):1393-6."
],
"codeine": [
"Impact of environmental and genetic factors on codeine analgesia. [ PMID 1782973 ] Desmeules J, Gascon MP, Dayer P, Magistris M. Eur J Clin Pharmacol 1991;41(1):23-26."
],
"debrisoquine": [
"Polymorphism of carbon oxidation of drugs and clinical implications. [ PMID 151576 ] Sloan TP, Mahgoub A, Lancaster R, Idle JR, Smith RL. Br Med J. 1978 Sep 2; 2(6138): 655-657.",
"Genetically determined defects of oxidation at carbon centers of drugs. [ PMID 76883 ] Smith RL, Idle JR, Mahgoub AA, Sloan TP, Lancaster R. Lancet. 1978 Apr 29; 1(8070): 943-944.",
"Hypotensive response to debrisoquine and hydroxylation phenotype. [ PMID 642709 ] Idle JR, Mahgoub A, Lancaster R, Smith RL. Life Sci. 1978 Mar; 22(11): 979-983.",
"Polymorphic hydroxylation of Debrisoquine in man. [ PMID 71400 ] Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL. Lancet. 1977 Sep 17; 2(8038): 584-586."
],
"desipramine": [
"Polymorphic 2-hydroxylation of desipramine: A population and family study. [ PMID 8359181 ] Dahl ML, Iselius L, Alm C, Svensson JO, Lee D, Johansson I. Ingelman-Sundberg M. Sjoqvist F. Eur J Clin Pharmacol 1993;44:445-450."
],
"dexfenfluramine": [
"The influence of the sparteine/debrisoquine genetic polymorphism on the disposition of dexfenfluramine. [ PMID 8730977 ] Gross AS, Phillips AC, Rieutord A, Shenfield GM. Br J Clin Pharmacol 1996;41:311-317."
],
"dextromethorphan": [
"Debrisoquine and dextromethorphan phenotyping and antidepressant treatment. [ PMID 2020918 ] Perault MC, Bouquet S, Bertschy G, Vandel S, Chakroun R, Guibert S, Vandel B. Therapie 1991 Jan;46(1):1-3.",
"Doxepin inhibits CYP2D6 activity in vivo. [ PMID 15520506 ] Szewczuk-Boguslawska M, Kiejna A, Beszlej JA, Orzechowska-Juzwenko K, Milejski P. Pol J Pharmacol. 2004 Jul-Aug;56(4):491-4."
],
"donepezil": [
"Donepezil in Alzheimer's disease: From conventional trials to pharmacogenetics. [ PMID 19300564 ] Cacabelos R. Neuropsychiatr Dis Treat. 2007 Jun;3(3):303-33.",
"Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer's disease patients. [ PMID 16845507 ] Varsaldi F, Miglio G, Scordo MG, Dahl ML, Villa LM, Biolcati A, Lombardi G. Eur J Clin Pharmacol. 2006 Sep;62(9):721-6."
],
"duloxetine": [
"Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. [ PMID 12621382 ] Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD. Clin Pharmacol Ther. 2003 Mar;73(3):170-7."
],
"encainide": [
"Effect of low dose quinidine on encainide pharmacokinetics and pharmacodynamics. Influence of genetic polymorphism. [ PMID 2496225 ] Funck-Brentano C, Turgeon J, Woosley RL, Roden DM. J Pharmacol Exp Ther 1989 Apr;249(1):134-42."
],
"flecainide": [
"Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. [ PMID 8143391 ] Funck-Brentano C, Becquemont L, Kroemer HK, Buhl K, Knebel NG, Eichelbaum M, Jaillon P. Clin Pharmacol Ther 1994 Mar;55(3):256-269."
],
"fluoxetine": [
"The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. [ PMID 8941024 ] Hamelin BA, Turgeon J, Vallee F, Belanger P-M, Paquet F, LeBel M. Clin Pharmacol Ther 1996;60:512-521."
],
"fluvoxamine": [
"Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. [ PMID 8823236 ] Carillo JA, Dahl M-L, Svennson J-O, Alm C, Rodriguez I, Bertillson L. Clin Pharmacol Ther 1996;60:183-190."
],
"histamine h1 receptor antagonists": [
"In Vitro Characterization of Cytochrome P450 2D6 Inhibition by Classic Histamine H1 Receptor Antagonists. [ PMID 9616188 ] Drug Metab Dispos. 1998 Jun;26(6):536-9."
],
"haloperidol": [
"Haloperidol disposition is dependent on the debrisoquine hydroxylation phenotype: increased plasma levels of the reduced metabolite in poor metabolizers. [ PMID 1412613 ] Llerena, A., Dahl, M.-L., Ekqvist, B., and Bertilsson, L. Ther Drug Monit 14:261-264, 1992."
],
"imipramine": [
"Role of P450 IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine. [ PMID 2060250 ] Brøsen K, Zeugin T, Meyer UA. Clin Pharmacol Ther 1991;49(6):609-617."
],
"lidocaine": [
"The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine. [ PMID 8422740 ] Ujhelyi MR, O'Rangers EA, Fan C, Kluger J, Pharand C, Chow MS. Clin Pharmacol Ther. 1993 Jan;53(1):38-48."
],
"metoclopramide": [
""
],
"methoxyamphetamine": [
""
],
"s-metoprolol": [
"Influence of amino acid residue 374 of cytochrome P-450 2D6 (CYP2D6) on the regio- and enantio-selective metabolism of metoprolol. [ PMID 8687412 ] Ellis SW, Rowland K, Ackland MJ, Rekka E, Simula AP, Lennard MS, Wolf CR, Tucker GT. Biochem J. 1996 Jun 1; 316( Pt 2): 647-654.",
"Influence of debrisoquine oxidation phenotype on exercise tolerance and subjective fatigue after metoprolol and atenolol in healthy subjects. [ PMID 2049246 ] Lewis RV, Ramsay LE, Jackson PR, Yeo WW, Lennard MS, Tucker GT. Br J Clin Pharmacol 1991 Apr;31(4):391-398.",
"Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers. [ PMID 1848636 ] Jonkers RE, Koopmans RP, Portier EJ, van Boxtel CJ. J Pharmacol Exp Ther 1991 Mar;256(3):959-966.",
"Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. [ PMID 2874665 ] Lennard MS, Tucker GT, Silas JH, Woods HF. Xenobiotica 1986 May;16(5):435-447.",
"Single-dose quinidine treatment inhibits metoprolol oxidation in extensive metabolizers. [ PMID 3709620 ] Leemann T, Dayer P, Meyer UA. Eur J Clin Pharmacol 1986;29(6):739-741.",
"Metoprolol metabolism and debrisoquine oxidation polymorphism--population and family studies. [ PMID 2868742 ] McGourty JC, Silas JH, Lennard MS, Tucker GT, Woods HF. Br J Clin Pharmacol 1985 Dec;20(6):555-566.",
"Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. [ PMID 6641087 ] Lennard MS, Tucker GT, Silas JH, Freestone S, Ramsay LE, Woods HF. Clin Pharmacol Ther 1983 Dec;34(6):732-737.",
"Oxidation phenotype--a major determinant of metoprolol metabolism and response. [ PMID 7144837 ] Lennard MS, Silas JH, Freestone S, Ramsay LE, Tucker GT, Woods HF. N Engl J Med 1982 Dec 16;307(25):1558-1560.",
"Defective metabolism of metoprolol in poor hydroxylators of debrisoquine. [ PMID 6125207 ] Lennard MS, Silas JH, Freestone S, Trevethick J. Br J Clin Pharmacol 1982 Aug;14(2):301-303."
],
"mexiletine": [
""
],
"minaprine": [
"Involvement of the cytochrome P-450IID subfamily in minaprine 4-hydroxylation by human hepatic microsomes. [ PMID 1352227 ] Marre F, Fabre G, Lacarelle B, Bourrie M, Catalin J, Berger Y, Rahmani R, Cano J. Drug Metab Dispos 20(2):316-321, 1992."
],
"nebivolol": [
"Pharmacokinetic disposition of nebivolol in extensive and poor CYP2D6 metabolizers. Andrew A. Shaw, John Ziemniak, Shiyao Liu, Scott W. Chervenick, Russell J. Rackley. American Society for Clinical Pharacology and Therapeutics. March 2-6, 2005. Orlando, FL."
],
"nortriptyline": [
""
],
"ondansetron": [
""
],
"oxycodone": [
""
],
"paroxetine": [
""
],
"perhexiline": [
""
],
"perphenazine": [
"Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. [ PMID 2743709 ] Dahl-Puustinen, M.-L., Liden, A., Alm, C., Nordin, C., and Bertilsson, L. Clin Pharmacol Ther 46(1):78-81, 1989.",
"Steady state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. [ PMID 8689810 ] Linnet K, Wiborg O. Clin Pharmacol Ther 1996;60:41-47.",
"Inhibitors of imipramine metabolism by human liver microsomes. [ PMID 1389950 ] Skjelbo, E. and Brosen, K. Br J Clin Pharmacol 34:256-261, 1992."
],
"phenacetin": [
""
],
"phenformin": [
""
],
"promethazine": [
"Akathisia with combined use of midodrine and promethazine. [ PMID 16670408 ] Platts SH, Shi SJ, Meck JV. JAMA. 2006 May 3;295(17):2000-1."
],
"propafenone": [
"The role of genetically-determined polymorphic drug metabolism in the beta-blockade produced by propafenone. [ PMID 1971708 ] Lee JT, Kroemer HK, Silberstein DJ, Funck-Brentano C, Lineberry MD, Wood AJJ, Roden DM, Woosley RL. N Eng J Med 1990;332(25):1764-1768."
],
"propanolol": [
""
],
"quanoxan": [
""
],
"risperidone": [
"Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. [ PMID 7690693 ] Huang ML, Van Peer A, Woestenborghs R, De Coster R, Heykants J, Jansen AA, Zylicz Z, Visscher HW, Jonkman JH. Clin Pharmacol Ther. 1993 Sep; 54(3): 257-268."
],
"sparteine": [
"Pharmacogenetic covariation of defective N-oxidation of sparteine and 4-hydroxylation of debrisoquine. [ PMID 7371707 ] Bertilsson L, Dengler HJ, Eichelbaum M, Schulz HU. Eur J Clin Pharmacol. 1980 Feb; 17(2): 153-155.",
"Influence of the defective metabolism of sparteine on its pharmacokinetics. [ PMID 499319 ] Eichelbaum M, Spannbrucker N, Dengler HJ. Eur J Clin Pharmacol. 1979 Sep; 16(3): 189-194.",
"Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. [ PMID 499318 ] Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ, Eur J Clin Pharmacol. 1979 Sep; 16(3): 183-187.",
"A human genetic defect in the metabolism of sparteine. [ PMID 741903 ] Spannbrucker N, Eichelbaum M, Steinke B, Dengler HJ. Verh Dtsch Ges Inn Med. 1978; 84: 1125-1127 German."
],
"tamoxifen": [
"Delineation of human cytochromes P450 involved in the metabolism of tamoxifen. Daniels L, Blankson EA, Henderson CJ, Harris AH, Wolf CR, Lennard MS, Tucker GT. Br J Clin Pharmacol 33:153P, 1992.",
"Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. [ PMID 14652237 ] Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. J Natl Cancer Inst. 2003 Dec 3;95(23):1734-5."
],
"thioridazine": [
"Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype. [ PMID 2007317 ] von Bahr C, Movin G, Nordon C, Liden A, Hammarlund-Udenaes,M, Hedberg,A, Ring H, Sjoqvist F. Clin Pharmacol Ther 49:234-240, 1991."
],
"timolol": [
"Pharmacogenetic explanation for excessive beta-blockade following timolol eye drops. Potential for oral-ophthalmic drug interaction. [ PMID 7474246 ] Edeki TI, He H, Wood AJ. JAMA. 1995 Nov 22; 274(20): 1611-1613.",
"Systemic absorption of ocular timolol in poor and extensive metabolizers of debrisoquine. [ PMID 1919275 ] Huupponen R, Kaila T, Lahdes K, Salminen L, Iisalo E. J Ocul Pharmacol. 1991; 7(2): 183-187.",
"The effects of timolol on intraocular pressure and exercise heart rate in poor and extensive debrisoquine metabolizers. [ PMID 2099359 ] al-Sereiti MR, Edeki T, Lledo P, Turner P. Int J Clin Pharmacol Res 1990;10(6):339-345.",
"Prevalence of debrisoquine oxidation phenotypes in glaucoma patients. [ PMID 2787298 ] Salminen L, Lindberg R, Toivari HR, Huupponen R, Kaila T, Iisalo E. Int Ophthalmol 1989 Jan;13(1-2):91-93.",
"Debrisoquine polymorphism and the metabolism and action of metoprolol, timolol, propranolol and atenolol. [ PMID 2874665 ] Lennard MS, Tucker GT, Silas JH, Woods HF. Xenobiotica. 1986 May; 16(5): 435-447.",
"Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin. [ PMID 2864157 ] McGourty JC, Silas JH, Fleming JJ, McBurney A, Ward JW. Clin Pharmacol Ther. 1985 Oct; 38(4): 409-413.",
"Timolol and atenolol: relationships between oxidation phenotype, pharmacokinetics and pharmacodynamics. [ PMID 2859048 ] Lewis RV, Lennard MS, Jackson PR, Tucker GT, Ramsay LE, Woods HF. Br J Clin Pharmacol. 1985 Mar; 19(3): 329-333.",
"Timolol determination in plasma and urine by high-performance liquid chromatography with ultraviolet detection. [ PMID 4019651 ] Lennard MS, Parkin S. J Chromatogr. 1985 Feb 27; 338(1): 249-252.",
"Polymorphic metabolism of the beta-adrenoreceptor blocking drugs and its clinical relevance [ PMID 2865154 ] Smith RL. Eur J Clin Pharmacol. 1985; 28 Suppl: 77-84."
],
"tramadol": [
"Pharmacology of tramadol. [ PMID 9190321 ] Dayer P, Desmeules J, Collart L. Drugs 1997;53 Suppl 2:18-24.",
"A rapid and simple CYP2D6 genotyping assay--case study with the analgetic tramadol. [ PMID 14624403 ] Borlak J, Hermann R, Erb K, Thum T. Metabolism. 2003 Nov;52(11):1439-43."
],
"venlafaxine": [
"O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. [ PMID 10192828 ] Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ. Neuropsychopharmacology 1999 May;20(5):480-90."
],
"zuclopenthixol": [
"Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? [ PMID 12083975 ] Dahl ML. Clin Pharmacokinet. 2002;41(7):453-70.",
"Pharmacogenetics of classical and new antipsychotic drugs. [ PMID 10688273 ] Otani K, Aoshima T. Ther Drug Monit. 2000 Feb;22(1):118-21.",
"Inhibitors Begin",
""
]
},
"inducers": {
"dexamethasone": [
""
]
},
"inhibitors": {
"amiodarone": [
"Effect of amiodarone on the serum concentration/dose ratio of metoprolol in patients with cardiac arrhythmia. [ PMID 17220566 ] Fukumoto K, Kobayashi T, Tachibana K, Kato R, Tanaka K, Komamura K, Kamakura S, Kitakaze M, Ueno K. Drug Metab Pharmacokinet. 2006 Dec;21(6):501-5.",
"Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. [ PMID 10718780 ] Ohyama K, Nakajima M, Suzuki M, Shimada N, Yamazaki H, Yokoi T. Br J Clin Pharmacol. 2000 Mar;49(3):244-53.",
"The inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O-demethylation in human and rat liver microsomes. [ PMID 7897605 ] Jaruratanasirikul S, Hortiwakul R. J Pharm Pharmacol. 1994 Nov;46(11):933-5."
],
"bupropion": [
"Inhibition of CYP2D6 activity by bupropion. [ PMID 15876900 ] Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE. J Clin Psychopharmacol. 2005 Jun;25(3):226-9."
],
"celecoxib": [
"Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. [ PMID 12891223 ] Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K. Clin Pharmacol Ther. 2003 Aug;74(2):130-7."
],
"cimetidine": [
"The effect of cimetidine on dextromethorphan O-demethylase activity of human liver microsomes and recombinant CYP2D6. [ PMID 16680870 ] Madeira M, Levine M, Chang TK, Mirfazaelian A, Bellward GD. Drug Metab Dispos. 2004 Apr;32(4):460-7.",
"Differential inhibition of individual human liver cytochromes P450 by cimetidine. [ PMID 1955133 ] Knodell RG, Browne DG, Gwozdz GP, Brian WR, Guengerich FP. Gastroenterology 1991;101:1680-1691."
],
"cinacalcet": [
"Effect of cinacalcet hydrochloride, a new calcimimetic agent, on the pharmacokinetics of dextromethorphan: in vitro and clinical studies. [ PMID 17652181 ] Nakashima D, Takama H, Ogasawara Y, Kawakami T, Nishitoba T, Hoshi S, Uchida E, Tanaka H. J Clin Pharmacol. 2007 Oct;47(10):1311-9.",
"Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. [ PMID 16680561 ] Harris RZ, Salfi M, Posvar E, Hoelscher D, Padhi D. Eur J Clin Pharmacol. 2007 Feb;63(2):159-63."
],
"citalopram": [
"Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. [ PMID 9068931 ] Preskorn SH. Clin Pharmacokinet. 1997;32 Suppl 1:1-21."
],
"clomipramine": [
"Cytochrome p450 IID6, its role in psychopharmacology. [ PMID 7741408 ] Lamard L, Perault MC, Bouquet S, Guibert S. Ann Med Psychol (Paris) 1995 Feb;153(2):140-143."
],
"cocaine": [
"Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): Potent inhibition of activity by (-)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. [ PMID 1857341 ] Tyndale RF, Sunahara RK, Inaba T, Kalow W, Gonzalez FJ, Niznik HB. Mol Pharmacol 40:63-68, 1991."
],
"doxorubicine": [
"Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. [ PMID 8258200 ] Le Guellec C, Lacarelle B, Catalin J, Durand A. Cancer Chemother Pharmacol 32:491-495, 1993."
],
"duloxetine": [
"Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers. [ PMID 12621382 ] Skinner MH, Kuan HY, Pan A, Sathirakul K, Knadler MP, Gonzales CR, Yeo KP, Reddy S, Lim M, Ayan-Oshodi M, Wise SD. Clin Pharmacol Ther. 2003 Mar;73(3):170-7."
],
"escitalopram": [
"Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. [ PMID 17224709 ] Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T. J Clin Psychopharmacol. 2007 Feb;27(1):28-34."
],
"fluoxetine": [
"Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance. [ PMID 10583026 ] Brynne N, Svanström C, Aberg-Wistedt A, Hallén B, Bertilsson L. Br J Clin Pharmacol. 1999 Oct;48(4):553-63.",
"Inhibitory effects of psychotropic drugs on mexiletine metabolism in human liver microsomes: prediction of in vivo drug interactions. [ PMID 16192107 ] Hara Y, Nakajima M, Miyamoto KI, Yokoi T. Xenobiotica. 2005 Jun;35(6):549-60."
],
"halofantrine": [
"Halofantrine and chloroquine inhibit CYP2D6 activity in healthy Zambians. [ PMID 10896408 ] Simooya OO, Sijumbil G, Lennard MS, Tucker GT. Br J Clin Pharmacol. 1998 Mar;45(3):315-7.",
"An investigation of the interaction between halofantrine, CYP2D6 and CYP3A4: studies with human liver microsomes and heterologous enzyme expression systems. [ PMID 8554939 ] Halliday RC, Jones BC, Smith DA, Kitteringham NR, Park BK. Br J Clin Pharmacol. 1995 Oct;40(4):369-78."
],
"histamine h1 receptor antagonists": [
"Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. [ PMID 17089107 ] Saruwatari J, Matsunaga M, Ikeda K, Nakao M, Oniki K, Seo T, Mihara S, Marubayashi T, Kamataki T, Nakagawa K. Eur J Clin Pharmacol. 2006 Dec;62(12):995-1001."
],
"levomepromazine": [
"O-demethylation of codeine to morphine inhibited by low-dose levomepromazine. [ PMID 19308365 ] Vevelstad M, Pettersen S, Tallaksen C, Brørs O. Eur J Clin Pharmacol. 2009 Mar 24."
],
"midodrine": [
"Akathisia with combined use of midodrine and promethazine. [ PMID 16670408 ] Platts SH, Shi SJ, Meck JV. JAMA. 2006 May 3;295(17):2000-1."
],
"methadone": [
"Inhibition of human cytochrome P450 2D6 (CYP2D6) by methadone. [ PMID 8448065 ] Wu D, Otton SV, Sproule BA, Busto U, Inaba T, Kalow W, Sellers EM. Br J Clin Pharmacol 1993 Jan;35(1):30-34."
],
"moclobemide": [
"Moclobemide: a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6 and CYP1A2: A panel study. [ PMID 7781267 ] Gram LF, Guentert TW, Grange S, Vistisen K, Brøsen K. Clin Pharmacol Ther 1995;57(6):670-677."
],
"paroxetine": [
"Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine. [ PMID 12584155 ] Bertelsen KM, Venkatakrishnan K, Von Moltke LL, Obach RS, Greenblatt DJ. Drug Metab Dispos. 2003 Mar;31(3):289-93.",
"CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. [ PMID 15632378 ] Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9.",
"Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. [ PMID 14652237 ] Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. J Natl Cancer Inst. 2003 Dec 3;95(23):1758-64.",
"Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. [ PMID 8513845 ] Brosen K, Hansen JG, Nielsen KK, Sindrup SH, Gram LF. Eur J Clin Pharmacol 44:349-355, 1993.",
"Plasma concentrations of clozapine and its major metabolites during combined treatment with paroxetine or sertraline. [ PMID 11147928 ] Spina E, Avenoso A, Salemi M, Facciolá G, Scordo MG, Ancione M, Madia A. Pharmacopsychiatry. 2000 Nov;33(6):213-7.",
"CYP2D6 inhibition by selective serotonin reuptake inhibitors: analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6. [ PMID 12173784 ] Lam YW, Gaedigk A, Ereshefsky L, Alfaro CL, Simpson J. Pharmacotherapy. 2002 Aug;22(8):1001-6."
],
"quinidine": [
"Why is quinidine an inhibitor of cytochrome P450 2D6? The role of key active-site residues in quinidine binding. [ PMID 16162505 ] McLaughlin LA, Paine MJ, Kemp CA, Maréchal JD, Flanagan JU, Ward CJ, Sutcliffe MJ, Roberts GC, Wolf CR. J Biol Chem. 2005 Nov 18;280(46):38617-24.",
"Inhibition of desmethylimipramine 2-hydroxylation by drugs in human liver microsomes. [ PMID 4015690 ] von Bahr C, Spina E, Birgersson C, Ericsson O, Göransson M, Henthorn T, Sjöqvist F. Biochem Pharmacol. 1985 Jul 15;34(14):2501-5.",
"In vivo modulation of CYP enzymes by quinidine and rifampin. [ PMID 11061580 ] Branch RA, Adedoyin A, Frye RF, Wilson JW, Romkes M. Clin Pharmacol Ther. 2000 Oct;68(4):401-11.",
"Inhibition of desipramine hydroxylation (Cytochrome P450-2D6) in vitro by quinidine and by viral protease inhibitors: relation to drug interactions in vivo. [ PMID 9758674 ] von Moltke LL, Greenblatt DJ, Duan SX, Daily JP, Harmatz JS, Shader RI. J Pharm Sci. 1998 Oct;87(10):1184-9."
],
"reduced haloperidol": [
"Oxidation of reduced haloperidol to haloperidol: involvement of human P450 2D6. [ PMID 1867960 ] Tyndale RF, Kalow W, Inaba T. Br J Clin Pharmacol 1991;31:655-660."
],
"ritonavir": [
"Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. [ PMID 8613951 ] Kumar GN, Rodrigues AD, Buko AM, Denissen JF. J Pharmacol Exp Ther 1996;277(1):423-431."
],
"sertraline": [
"Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. [ PMID 17224709 ] Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T. J Clin Psychopharmacol. 2007 Feb;27(1):28-34.",
"The effect of sertraline on the pharmacokinetics of desipramine and imipramine. [ PMID 9284850 ] Kurtz DL, Bergstrom RF, Goldberg MJ, Cerimele BJ. Clin Pharmacol Ther. 1997 Aug;62(2):145-56."
],
"terbinafine": [
"Potent inhibition of cytochrome P-450 2D6-mediated dextromethorphan O-demethylation by terbinafine. [ PMID 10383919 ] Abdel-Rahman SM, Marcucci K, Boge T, Gotschall RR, Kearns GL, Leeder JS. Drug Metab Dispos. 1999 Jul;27(7):770-5."
]
}
},
"2c19": {
"substrates": {
"cyp2c19 itself": [
"Isolation and Characterization of Human Liver Cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4'-hydroxylation. [ PMID 8215410 ] Wrighton SA, Stevens JC, Becker GW and Vandenbranden M. Pubmed Biochem Biophys 1993 Oct;306(1):240-245."
],
"amitriptyline": [
"Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. [ PMID 9549641 ] Venkatakrishnan K, Greenblatt DJ, von Moltke LL, Schmider J, Harmatz JS, Shader RI. Clin Pharmacol. 1998 Feb; 38(2): 112-121.",
"Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. [ PMID 9399333 ] Olesen OV, Linnet K. Pharmacology. 1997 Nov; 55(5): 235-243.",
"Cytochromes P450 mediating the N-demethylation of amitriptyline. [ PMID 9131945 ] Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT. Br J Clin Pharmacol. 1997 Feb; 43(2): 137-144."
],
"carisoprodol": [
""
],
"chloramphenicol": [
"Chloramphenicol Is a Potent Inhibitor of Cytochrome P450 Isoforms CYP2C19 and CYP3A4 in Human Liver Microsomes. [ PMID 14576103 ] Park JY, Kim KA, Kim SL. Antimicrob Agents Chemother. 2003 Nov;47(11):3464-9."
],
"citalopram": [
"Personal communication with Dr. Terence Ketter about citalopram on March 29, 1995. Ketter, TA. Flockhart, DA 1995."
],
"clomipramine": [
"Pharmacogenetics of antidepressants: clinical aspects. [ PMID 9265947 ] Bertilsson L, Dahl ML, Tybring G. Acta Psychiatr Scand Suppl 1997;391:14-21."
],
"clopidogrel": [
"The Effect of CYP2C19 Polymorphism on the Pharmacokinetics and Pharmacodynamics of Clopidogrel: A Possible Mechanism for Clopidogrel Resistance. [ PMID 18323861 ] Kim K, Park P, Hong S, Park JY. Clin Pharmacol Ther. 2008 Aug;84(2):236-42.",
"Genetic determinants of response to clopidogrel and cardiovascular events. [ PMID 19106083 ] Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, Ferrières J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. N Engl J Med. 2009 Jan 22;360(4):363-75."
],
"cyclophosphamide": [
"Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. [ PMID 9241661 ] Chang TKH, Yu L, Goldstein JA, Waxman DJ. Pharmacogenetics 1997;7:211-221."
],
"diazepam": [
"Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N-demethylation in the substrate concentration-dependent manner. [ PMID 8148870 ] Yasumori T, Nagata K, Yang SK, Chen L-S, Murayama N, Yamazoe Y, Kato R. Pharmacogenetics 1993;3:291-301."
],
"escitalopram": [
""
],
"hexobarbital": [
"Stereoselective disposition of hexobarbital and its metabolites: relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. [ PMID 8004130 ] Adedoyin A, Prakash C, O'Shea D, Blair IA, Wilkinson GR. Pharmacogenetics. 1994 Feb; 4(1): 27-38.",
"Polymorphism in stereoselective hydroxylations of mephenytoin and hexobarbital by Japanese liver samples in relation to cytochrome P-450 human-2 (IIC9). [ PMID 1441599 ] Kato R, Yamazoe Y, Yasumori T. Xenobiotica. 1992 Sep; 22(9-10): 1083-1092. Review.",
"Polymorphism in hydroxylation of mephenytoin and hexobarbital stereoisomers in relation to hepatic P-450 human-2. [ PMID 2311333 ] Yasumori T, Murayama N, Yamazoe Y, Kato R. Clin Pharmacol Ther. 1990 Mar; 47(3): 313-322.",
"Oxidative metabolism of hexobarbital in human liver: relationship to polymorphic S-mephenytoin 4-hydroxylation. [ PMID 3385644 ] Knodell RG, Dubey RK, Wilkinson GR, Guengerich FP. J Pharmacol Exp Ther. 1988 Jun; 245(3): 845-849."
],
"imipramine n-deme": [
"Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. [ PMID 9190854 ] Koyama E, Chiba K, Tani M, Ishizaki T. J Pharmacol Exp Ther. 1997 Jun; 281(3): 1199-1210.",
"Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. [ PMID 8521680 ] Bertilsson L. Clin Pharmacokinet. 1995 Sep; 29(3): 192-209. Review."
],
"indomethacin": [
"Human cytochrome P4502C metabolism. Weaver RJ, Webster D, Melvin WT, Dickins M and Burke MD. Br J Clin Pharmacol 1993 April;36(2):167P."
],
"lansoprazole": [
"Metabolic disposition of lansoprazole in relation to the S-mephenytoin 4'-hydroxylation phenotype status. [ PMID 9164419 ] Sohn DR, Kwon JT, Kim HK, Ishizaki T. Clin Pharmacol Ther 1997 May;61(5):574-582."
],
"s-mephenytoin": [
"Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. [ PMID 6499356 ] Wedlund PJ, Aslanian WS, McAllister CB, Wilkinson GR, Branch RA. Clin Pharmacol Ther, 1984 Dec; 36(6):773-780."
],
"r-mephobarbital": [
"Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. [ PMID 4042524 ] Kupfer A, Branch RA. Clin Pharmacol Ther, 1985 Oct; 38(4):414-418."
],
"moclobemide": [
"Moclobemide: a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6 and CYP1A2: A panel study. [ PMID 7781267 ] Gram LF, Guentert TW, Grange S, Vistisen K, Brøsen K. Clin Pharmacol Ther 1995;57(6):670-677."
],
"nelfinavir": [
"Characterization of the selectivity and mechanism of human cytochrome P450 inhibition by the human immunodeficiency virus-protease inhibitor nelfinavir mesylate. [ PMID 9660842 ] Lillibridge JH, Liang BH, Kerr BM, Webber S, Quart B, Shetty BV, Lee CA. Drug Metab Dispos 1998 Jul;26(7):609-16."
],
"nilutamide": [
"Nilutamide inhibits mephenytoin 4-hydroxylation in untreated male rats and in human liver microsomes. [ PMID 1785203 ] Horsmans Y, Lannes D, Larrey D, Tinel M, Letteron P, Loeper J, Pessayre D. Xenobiotica 1991 Dec;21(12):1559-1570."
],
"omeprazole": [
"Effect of omeprazole on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. [ PMID 2104790 ] Andersson T, Cederberg C, Edvardsson G, Heggelund A, Lundborg P. Clin Pharmacol Ther 1990;47(1):79-85."
],
"oxcarbazepine": [
"Spotlight on oxcarbazepine in epilepsy. [ PMID 14731060 ] Bang LM, Goa KL. CNS Drugs. 2004;18(1):57-61."
],
"pantoprazole": [
"Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype. [ PMID 9433390 ] Tanaka M, Ohkubo T, Otani K, Suzuki A, Kaneko S, Sugawara K, Ryokawa Y, Hakusui H, Yamamori S, Ishizaki T. Clin Pharmacol Ther 1997 Dec;62(6):619-628."
],
"phenytoin": [
"Role of S-mephenytoin hydroxylase in the metabolism of phenytoin. Bajpai M, Roskos LK, Shen DD, Trager WF, Levy RH. Pharm Res 1994, 11(Suppl):S348."
],
"phenobarbitone": [
"CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics. Mamiya K, Hadama A, Yukawa E, Ieiri I, Otsubo K, Ninomiya H, Tashiro N, Higuchi S. Eur J Clin Pharmacol 2000, 55:821-825."
],
"primidone": [
""
],
"progesterone": [
"Progesterone and testosterone hydroxylation by CYP 2C19, 2C9 and 3A4 in human liver microsomes. [ PMID 9328296 ] Yamazaki H, Shimada T. Arch Biochem Biophys 1997;346(1):161-169."
],
"proguanil": [
"Metabolic Disposition of proguanil in extensive and poor metabolizers of S-mephenytoin 4'-hydroxylation recruited from an Indonesian population. [ PMID 7619672 ] Setiabudy R, Kusaka M, Chiba K, Darmansjah I, Ishizaki T. Br J Clin Pharmacol 1995;39(3):297-303.",
"In vitro proguanil activation to cycloguanil by human liver microsomes is mediated by CYP3A isoforms as well as S-mephenytoin hydroxylase. [ PMID 8054246 ] Birkett DJ, Rees D, Andersson T, Gonzalex FJ, Miners JO, Veronese ME. Br J Clin Pharmacol 1994;37:413-420.",
"The activation of the biguanide anti-malarial proguanil co-segregates with the mephenytoin oxidation polymorphism - a panel study. [ PMID 1867963 ] Ward SA, Helsby NA, Skjelbo E, Brøsen K, Gram LF, Breckenridge AM. Br J Clin Pharmacol 1991;31:689-692.",
"Relation between chloroguanide bioavtivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans. [ PMID 1587064 ] Funck-Brentano C, Bosco O, Jacqz-Aigrain E, KeunjiN a, Jaillon P. Clin Pharmacol Ther 1992;51(5):507-512."
],
"propranolol": [
"Not in vitro. Propranolol oxidation by human liver microsomes-- use of cumene hydroperoxide to probe isoenzyme specificity and regio- and stereoselectivity. [ PMID 2271375 ] Otton SV, Gillam EM, Lennard MS, Tucker GT, Woods HF. Br J Clin Pharmacol 1990 Nov;30(5):751-760."
],
"rabeprazole": [
"Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced and standard doses: a crossover comparative study in homozygous extensive metabolizers of cytochrome P450 2C19. [ PMID 16413249 ] Shimatani T, Inoue M, Kuroiwa T, Xu J, Mieno H, Nakamura M, Tazuma S. Clin Pharmacol Ther. 2006 Jan;79(1):144-52."
],
"r-warfarin": [
"Correlation of human cytochrome P450 2C substrate specificities with primary structure: warfarin as a probe. [ PMID 8429826 ] Kaminsky LS, de Morais SM, Faletto MB, Dunbar DA, Goldstein JA. Mol Pharmacol 1993;43:234-239."
],
"teniposide": [
"Inhibitors Begin"
]
},
"inducers": {
"carbamazepine": [
""
],
"norethindrone": [
""
],
"not pentobarbital": [
"Influence of enzyme induction and inhibition on the oxidation of nifedipine, mephenytoin and antipyrine in humans as assessed by a \"cocktail\" study design. [ PMID 2724144 ] Schellens JHM, van der Wart JHF, Brugman M, Breimer DD. J Pharmac Exp Ther 1989;249(2):638-645."
],
"prednisone": [
"Influence of corticosteroid on hexobarbital and tolbutamide disposition. [ PMID 679598 ] Breimer DD, Zilly W, Richter E. Clin Pharmacol Ther 1978 Aug;24(2):208-212."
]
},
"inhibitors": {
"cimetidine": [
"Mechanism of warfarin potentiation by amiodarone: dose--and concentration-dependent inhibition of warfarin elimination. [ PMID 4007030 ] Almog S, Shafran N, Halkin H, Weiss P, Farfel Z, Martinowitz U, Bank H. Eur J Clin Pharmacol 1985;28:257-261."
],
"chloramphenicol": [
"Chloramphenicol Is a Potent Inhibitor of Cytochrome P450 Isoforms CYP2C19 and CYP3A4 in Human Liver Microsomes. [ PMID 14576103 ] Park JY, Kim KA, Kim SL. Antimicrob Agents Chemother. 2003 Nov;47(11):3464-9."
],
"felbamate": [
""
],
"fluoxetine": [
"Evaluation of time-dependent cytochrome P450 inhibition using cultured human hepatocytes. [ PMID 16679385 ] McGinnity DF, Berry AJ, Kenny JR, Grime K, Riley RJ. Drug Metab Dispos. 2006 Aug;34(8):1291-300.",
"Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers. [ PMID 11270912 ] Harvey AT, Preskorn SH. J Clin Psychopharmacol. 2001 Apr;21(2):161-6.",
"Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. [ PMID 8880055 ] Jeppesen U, Gram LF, Vistisen K, Loft S, Poulsen HE, Brøsen K. Eur J Clin Pharmacol. 1996;51(1):73-8.",
"The effects of selective serotonin reuptake inhibitors and their metabolites on S-mephenytoin 4'-hydroxylase activity in human liver microsomes. [ PMID 8703653 ] Kobayashi K, Yamamoto T, Chiba K, Tani M, Ishizaki T, Kuroiwa Y. Br J Clin Pharmacol. 1995 Nov;40(5):481-5."
],
"fluvoxamine": [
"Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. [ PMID 17596106 ] von Richter O, Lahu G, Huennemeyer A, Herzog R, Zech K, Hermann R. Clin Pharmacokinet. 2007;46(7):613-22.",
"Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. [ PMID 15025747 ] Yasui-Furukori N, Takahata T, Nakagami T, Yoshiya G, Inoue Y, Kaneko S, Tateishi T. Br J Clin Pharmacol. 2004 Apr;57(4):487-94.",
"Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients: interaction with CYP2C19 mutated alleles. [ PMID 12698310 ] Suzuki Y, Shioiri T, Muratake T, Kawashima Y, Sato S, Hagiwara M, Inoue Y, Shimoda K, Someya T. Eur J Clin Pharmacol. 2003 Apr;58(12):829-33."
],
"indomethacin": [
"Cytochrome P450 2C9 catalyzes indomethacin O-demethylation in human liver microsomes. [ PMID 9492390 ] Nakajima M, Inoue T, Shimada N, Tokudome S, Yamamoto T, Kuroiwa Y. Drug Metab Dispos. 1998 Mar;26(3):261-6."
],
"ketoconazole": [
"Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. [ PMID 14709627 ] Stresser DM, Broudy MI, Ho T, Cargill CE, Blanchard AP, Sharma R, Dandeneau AA, Goodwin JJ, Turner SD, Erve JC, Patten CJ, Dehal SS, Crespi CL. Drug Metab Dispos. 2004 Jan;32(1):105-12.",
"In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole. [ PMID 15618748 ] Emoto C, Murase S, Sawada Y, Jones BC, Iwasaki K. Drug Metab Pharmacokinet. 2003;18(5):287-95."
],
"lansoprazole": [
"Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. [ PMID 9224780 ] Ko JW, Sukhova N, Thacker D, Chen P, Flockhart DA. Eur J Clin Pharmacol 1985;28:257-261.",
"Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. [ PMID 15258107 ] Li XQ, Andersson TB, Ahlström M, Weidolf L. Drug Metab Dispos. 2004 Aug;32(8):821-7.",
"Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro. [ PMID 15788366 ] Liu KH, Kim MJ, Shon JH, Moon YS, Seol SY, Kang W, Cha IJ, Shin JG. Xenobiotica. 2005 Jan;35(1):27-38."
],
"modafinil": [
"In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil. [ PMID 10820139 ] Robertson P, DeCory HH, Madan A, Parkinson A. Drug Metab Dispos. 2000 Jun;28(6):664-71."
],
"omeprazole": [
"Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. [ PMID 9224780 ] Ko JW, Sukhova N, Thacker D, Chen P, Flockhart DA. Eur J Clin Pharmacol 1985;28:257-261."
],
"oxcarbazepine": [
"Spotlight on oxcarbazepine in epilepsy. [ PMID 14731060 ] Bang LM, Goa KL. CNS Drugs. 2004;18(1):57-61.",
"Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19. [ PMID 12458024 ] Lakehal F, Wurden CJ, Kalhorn TF, Levy RH. Epilepsy Res. 2002 Dec;52(2):79-83."
],
"pantoprazole": [
"Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4'-hydroxylation phenotype and genotype. [ PMID 9433390 ] Tanaka M, Ohkubo T, Otani K, Suzuki A, Kaneko S, Sugawara K, Ryokawa Y, Hakusui H, Yamamori S, Ishizaki T. Clin Pharmacol Ther 1997 Dec;62(6):619-628."
],
"probenicid": [
""
],
"rabeprazole": [
"Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced and standard doses: a crossover comparative study in homozygous extensive metabolizers of cytochrome P450 2C19. [ PMID 16413249 ] Shimatani T, Inoue M, Kuroiwa T, Xu J, Mieno H, Nakamura M, Tazuma S. Clin Pharmacol Ther. 2006 Jan;79(1):144-52.",
"Different effects of fluvoxamine on rabeprazole pharmacokinetics in relation to CYP2C19 genotype status. [ PMID 16487224 ] Uno T, Shimizu M, Yasui-Furukori N, Sugawara K, Tateishi T. Br J Clin Pharmacol. 2006 Mar;61(3):309-14."
],
"ticlopidine": [
"Interaction magnitude, pharmacokinetics and pharmacodynamics of ticlopidine in relation to CYP2C19 genotypic status. [ PMID 16272957 ] Ieiri I, Kimura M, Irie S, Urae A, Otsubo K, Ishizaki T. Pharmacogenet Genomics. 2005 Dec;15(12):851-9.",
"Ticlopidine decreases the in vivo activity of CYP2C19 as measured by omeprazole metabolism. [ PMID 10233213 ] Tateishi T, Kumai T, Watanabe M, Nakura H, Tanaka M, Kobayashi S. Br J Clin Pharmacol. 1999 Apr;47(4):454-7.",
"Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19. [ PMID 11580286 ] Ha-Duong NT, Dijols S, Macherey AC, Goldstein JA, Dansette PM, Mansuy D. Biochemistry. 2001 Oct 9;40(40):12112-22.",
"Ticlopidine inhibition of phenytoin metabolism mediated by potent inhibition of CYP2C19. [ PMID 9390115 ] Donahue SR, Flockhart DA, Abernethy DR, Ko JW. Clin Pharmacol Ther. 1997 Nov;62(5):572-7."
],
"topiramate": [
"Topiramate and phenytoin pharmacokinetics during repetitive monotherapy and combination therapy to epileptic patients. [ PMID 12102670 ] Sachdeo RC, Sachdeo SK, Levy RH, Streeter AJ, Bishop FE, Kunze KL, Mather GG, Roskos LK, Shen DD, Thummel KE, Trager WF, Curtin CR, Doose DR, Gisclon LG, Bialer M. Epilepsia. 2002 Jul;43(7):691-6."
]
}
},
"2e1": {
"substrates": {
"acetaminophen=>napqi": [
"Acetaminophen activation by human liver cytochrome P450 2E1 and 1A2. [ PMID 2729995 ] Raucy JE, Lasker JM, Lieber CS, Black M. Arch Biochem Biophys 1989;271(2):270-283."
],
"aniline": [
"Requirements for cytochrome b5 in the oxidation of 7-ethoxycoumarin, chlorzoxazone, aniline, and N-nitrosodimethylamine by recombinant cytochrome P450 2E1 and by human liver microsomes. [ PMID 8694855 ] Yamazaki H, Nakano M, Gillam EM, Bell LC, Guengerich FP, Shimada T. Biochem Pharmacol 1996 Jul 26;52(2):301-309."
],
"benzene": [
"Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone. [ PMID 9230185 ] Rothman N, Smith MT, Hayes RB, Traver RD, Hoener B, Campleman S, Li GL, Dosemeci M, Linet M, Zhang L, Xi L, Wacholder S, Lu W, Meyer KB, Titenko-Holland N, Stewart JT, Yin S, Ross D. Cancer Res 1997 Jul 15;57(14):2839-2842."
],
"chlorzoxazone": [
"Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P4502E1. [ PMID 2103328 ] Peter R, Böcker R, Beaune PH, Iwasaki PH,Guengerich FP, Yang CS. Chem Res Toxicol 1990;3:566-573."
],
"enflurane": [
"Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1. [ PMID 8689955 ] Garton KJ, Yuen P, Meinwald J, Thummel KE, Kharasch ED. Drug Metab Dispos 1995 Dec;23(12):1426-1430.",
"Clinical enflurane metabolism by cytochrome P450 2E1. [ PMID 8162670 ] Kharasch ED, Thummel KE, Mautz D, Bosse S. Clin Pharmacol Ther 1994 Apr;55(4):434-440."
],
"ethanol": [
""
],
"halothane": [
"Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. [ PMID 9103523 ] Spracklin DK, Hankins DC, Fisher JM, Thummel KE, Kharasch ED. J Pharmacol Exp Ther 1997 Apr;281(1):400-11.",
"Interindividual variability in P450-dependent generation of neoantigens in halothane hepatitis. [ PMID 9877205 ] Eliasson E, Gardner I, Hume-Smith H, de Waziers I, Beaune P, Kenna JG. Chem Biol Interact 1998 Nov 6;116(1-2):123-41."
],
"isoflurane": [
""
],
"methoxyflurane": [
""
],
"n,n-dimethylformamide": [
"Investigation of the mechanistic basis of N,N-dimethylformamide toxicity. Metabolism of N,N-dimethylformamide and its deuterated isotopomers by cytochrome P450 2E1. [ PMID 8477011 ] Mraz J, Jheeta P, Gescher A, Hyland R, Thummel K, Threadgill MD. Chem Res Toxicol 1993 Mar;6(2):197-207."
],
"sevoflurane": [
""
],
"theophylline": [
"Dose-dependent inhibition of theophylline metabolism by disulfiram in recovering alcoholics. [ PMID 2721103 ] Loi CM, Day JD, Jue SG, Bush ED, Costello P, Dewey LV, Vestal RE. Clin Pharmacol Ther 1989:45(5):476-486.",
"Inhibitors Begin",
""
]
},
"inducers": {
"ethanol": [
""
]
},
"inhibitors": {
"diethyl-dithiocarbamate": [
"Role of human cytochrome P450 2E1 in the oxidation of many low molecular weight cancer suspects. [ PMID 1664256 ] Guengerich FP, Kim DH, Iwasaki M. Chem Res Toxicol 1991; 4:168-179."
],
"disulfiram": [
"Single dose disulfiram inhibition of chlorzoxazone metabolism: A clinical probe for P450 2E1. [ PMID 8513656 ] Kharasch ED, Thummel KE, Mhyre J, Lillibridge JH. Clin Pharmacol Ther 1993;53:643-650."
]
}
},
"2c9": {
"substrates": {
"amitriptyline": [
"Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. [ PMID 9663807 ] Miners JO, Birkett DJ. Br J Clin Pharmacol 1998 Jun;45(6):525-38."
],
"celecoxib": [
"Cytochrome P450 2C9 Variants Influence Response to Celecoxib for Prevention of Colorectal Adenoma. [ PMID 19233181 ] Chan AT, Zauber AG, Hsu M, Breazna A, Hunter DJ, Rosenstein RB, Eagle CJ, Hawk ET, Bertagnolli MM. Gastroenterology. 2009 Feb 21.",
"Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. [ PMID 17681167 ] Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, Niro V, Andriulli A, Leandro G, Di Mario F, Dallapiccola B. Gastroenterology. 2007 Aug;133(2):465-71."
],
"not candesartan": [
"Candesartan cilexetil: a review of its preclinical pharmacology. [ PMID 9330999 ] Nishikawa K, Naka T, Chatani F, Yoshimura Y. J Hum Hypertens 1997 Sep;11 Suppl 2:S9-S17.",
"Pharmacokinetic drug interaction studies with candesartan cilexetil. [ PMID 9331003 ] Jonkman JH, van Lier JJ, van Heiningen PN, Lins R, Sennewald R, Hogemann A. J Hum Hypertens 1997 Sep;11 Suppl 2:S31-S35.",
"Absorption, metabolism and excretion of 14C-candesartan and 14C-candesartan cilexetil in healthy volunteers. [ PMID 9331001 ] van Lier JJ, van Heiningen PN, Sunzel M. J Hum Hypertens 1997 Sep;11 Suppl 2:S27-S28."
],
"diclofenac": [
"In vivo inhibition profile of cytochrome P450tb (CYP2C9) by (±)-fluvastatin. [ PMID 7586933 ] Transon C, Leemann T, Vogt N, Dayer P. Clin Pharmacol Ther 1995;58(4):412-417."
],
"fluoxetine": [
"Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. [ PMID 9663807 ] Miners JO, Birkett DJ. BrJ Clin Pharmacol 1998 Jun;45(6):525-38"
],
"fluvastatin": [
"The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. [ PMID 10064574 ] Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP, Robinson WT. Drug Metab Dispos 1999 Mar;27(3):410-6"
],
"glimepiride": [
"Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepiride in subjects with type 2 diabetes. [ PMID 16325295 ] Suzuki K, Yanagawa T, Shibasaki T, Kaniwa N, Hasegawa R, Tohkin M. Diabetes Res Clin Pract. 2006 May;72(2):148-54.",
"Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. [ PMID 12235454 ] Niemi M, Cascorbi I, Timm R, Kroemer HK, Neuvonen PJ, Kivistö KT. Clin Pharmacol Ther. 2002 Sep;72(3):326-32."
],
"glipizide": [
"Effects of rifampin on the pharmacokinetics and pharmacodynamics of glyburide and glipizide. [ PMID 11406737 ] Niemi M, Backman JT, Neuvonen M, Neuvonen PJ, Kivistö KT. Clin Pharmacol Ther. 2001 Jun;69(6):400-6.",
"Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. [ PMID 10208645 ] Kidd RS, Straughn AB, Meyer MC, Blaisdell J, Goldstein JA, Dalton JT. Pharmacogenetics. 1999 Feb;9(1):71-80."
],
"glyburide": [
"Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. [ PMID 11956512 ] Kirchheiner J, Brockmoller J, Meineke I, Bauer S, Rohde W, Meisel C, Roots I. Clin Pharmacol Ther 2002 Apr;71(4):286-96."
],
"glibenclamide": [
"Effects of clarithromycin and grapefruit juice on the pharmacokinetics of glibenclamide. [ PMID 17223855 ] Lilja JJ, Niemi M, Fredrikson H, Neuvonen PJ. Br J Clin Pharmacol. 2007 Jun;63(6):732-40.",
"Impact of cytochrome P450 CYP2C9 variant allele CYP2C9*3 on the pharmacokinetics of glibenclamide and lornoxicam in Chinese subjects. [ PMID 16342679 ] Zhang YF, Chen XY, Guo YJ, Si DY, Zhou H, Zhong DF. Yao Xue Xue Bao. 2005 Sep;40(9):796-9."
],
"ibuprofen": [
"Stereo- and nonstereospecific oxidation by P450tb (CYP2C): The major elimination pathway of (+/-) -ibuprofen. [ PMID 1462152 ] Leeman, T., Bonnabry, P., and Dayer, P. Clin Pharmacol Ther 55:208, 1994."
],
"irbesartan": [
"CYP2C9 Ile359Leu polymorphism, plasma irbesartan concentration and acute blood pressure reductions in response to irbesartan treatment in Chinese hypertensive patients. [ PMID 16541193 ] Chen G, Jiang S, Mao G, Zhang S, Hong X, Tang G, Li Z, Liu X, Zhang Y, Xing H, Wang B, Yu Y, Xu X. Methods Find Exp Clin Pharmacol. 2006 Jan-Feb;28(1):19-24.",
"Determinants of steady-state torasemide pharmacokinetics: impact of pharmacogenetic factors, gender and angiotensin II receptor blockers. [ PMID 18399713 ] Werner D, Werner U, Meybaum A, Schmidt B, Umbreen S, Grosch A, Lestin HG, Graf B, Zolk O, Fromm MF. Clin Pharmacokinet. 2008;47(5):323-32."
],
"lornoxicam": [
"Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in human. [ PMID 15764711 ] Guo Y, Zhang Y, Wang Y, Chen X, Si D, Zhong D, Fawcett JP, Zhou H. Drug Metab Dispos. 2005 Jun;33(6):749-53."
],
"lorsartan": [
"A mutation in CYP2C9 is responsible for decreased metabolism of losartan. [ PMID 10096267 ] Spielberg S, McCrea J, Cribb A, Rushmore T, Waldman SA. Bjornnson T, Lo M-W, Goldberg M. Clin Pharmacol Ther. 1999 Mar;65(3):348-52."
],
"meloxicam": [
"Metabolism of Meloxicam in human liver involves cytochromes P4502C9 and 3A4. [ PMID 9493314 ] Chesné C, Guyomard C, Guillouzo A, Schmid J, Ludwig E, Sauter T. Xenobiotica. 1998 Jan;28(1):1-13."
],
"naproxen": [
"Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. [ PMID 8866821 ] Miners JO, Coulter S, Tukey RH, Veronese ME, Birkett DJ. Biochem Pharmacol 1996 Apr 26;51(8):1003-1008."
],
"nateglinide": [
"Effect of rifampicin on the pharmacokinetics and pharmacodynamics of nateglinide in healthy subjects. [ PMID 12968988 ] Niemi M, Backman JT, Neuvonen M, Neuvonen PJ. Clin Pharmacol Ther. 2003 Oct;74(4):380-7."
],
"phenytoin": [
"Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. [ PMID 2025243 ] Veronese ME, Mackenzie PI, Doecke CJ, McManus ME, Miners JO, Birkett DJ. Biochem Biophys Res Commun. 1991;175(3):1112-1118.",
"Fluconazole-induced symptomatic phenytoin toxicity.[ PMID 8173131 ] Cadle RM, Zenon GJ III, Rodriguez-Barradas MC, Hamill RJ. Ann Pharmacother 1994;28(2) 191-194."
],
"piroxicam": [
"Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. [ PMID 9248768 ] Tracy TS, Marra C, Wrighton SA, Gonzalez FJ, Korzekwa KR. Eur J Clin Pharmacol. 1997; 52(4): 293-298.",
"Studies of flurbiprofen 4'-hydroxylation. Additional evidence suggesting the sole involvement of cytochrome P450 2C9. [ PMID 8937439 ] Tracy TS, Marra C, Wrighton SA, Gonzalez FJ, Korzekwa KR. Biochem Pharmacol. 1996 Oct 25; 52(8): 1305-1309."
],
"rosiglitazone": [
"Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. [ PMID 12898007 ] Niemi M, Backman JT, Granfors M, Laitila J, Neuvonen M, Neuvonen PJ. Diabetologia. 2003 Oct;46(10):1319-23.",
"Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects. [ PMID 15373932 ] Park JY, Kim KA, Shin JG, Lee KY. Br J Clin Pharmacol. 2004 Oct;58(4):397-402."
],
"suprofen": [
"The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling. [ PMID 7654690 ] Mancy A, Broto P, Dijols S, Dansette PM, Mansuy D. Biochemistry 1995 Aug 22;34(33):10365-10375."
],
"tamoxifen": [
"Delineation of human cytochromes P450 involved in the metabolism of tamoxifen. Daniels, L, Blankson, EA, Henderson, CJ, Harris, AH, Wolf, CR, Lennard, MS, and Tucker, GT. Br J Clin Pharmacol 33:153P, 1992."
],
"torsemide": [
"Human hepatic Cytochrome P450 catalyses the rate-limiting pathway of torsemide metabolism. [ PMID 7891318 ] Miners JO, Rees DLP, Valente L, Veronese ME, Birkett DJ. J Pharmacol Exp Ther 1995;272(3):1076-1081."
],
"tolbutamide": [
"Putative active site template model for cytochrome P4502C9 (Tolbutamide hydroxylase). [ PMID 8742240 ] Jones BC, Hawksworth G, Horne VA, Newlands A, Morsman J, Tute MS, Smith DA. Drug Metabolism and Disposition 1996;24(2):260-266."
],
"not valsartan": [
"Pharmacokinetics of valsartan in patients with liver disease. [ PMID 9333102 ] Brookman LJ, Rolan PE, Benjamin IS, Palmer KR, Wyld PJ, Lloyd P, Flesch G, Waldmeier F, Sioufi A, Mullins F. Clinical Pharmacology and Therapeutics, 62 (3) 272-278 1997."
],
"s-warfarin": [
"Possible interaction between warfarin and fluconazole. [ PMID 8247921 ] Gericke KR. Pharmacotherapy 1993;13(5):508-509.",
"Possible potentiation of warfarin by fluconazole. [ PMID 2089826 ] Seaton TL, Celum C.L., Black DJ. Drug Intelligence Clin Pharmacol 1990;24:1177-1178.",
"Interactions of warfarin with drugs and food. [ PMID 7944078 ] Wells PS, Holbrook AM, Crowther NR, Hirsh J. Ann Intern Med 1994;121:676-683.",
"Inhibition of the human cytochrome P450- dependent metabolism of warfarin by fluconazole: in vitro studies. [ PMID 8801056 ] Kunze KL, Wienkers LC, Thummel KE, Trager WF. Drug Metab Dispos 1996;24(4):414-421.",
"A metabolically based drug interaction between fluconazole and warfarin: in vivo studies. [ PMID 8801057 ] Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, McDonnell ND, Evans JS, Bauwens JE, Trager WF. Drug Metab Dispos 1996;24(4):422-428."
]
},
"inducers": {
"rifampin": [
""
]
},
"inhibitors": {
"fenofibrate": [
"Fenofibrate potentiates warfarin effects. [ PMID 12549950 ] Kim KY, Mancano MA. Ann Pharmacother. 2003 Feb;37(2):212-5."
],
"amiodarone": [
"Mechanism of warfarin potentiation by amiodarone: dose--and concentration-dependent inhibition of warfarin elimination. [ PMID 4007030 ] Almog S, Shafran N, Halkin H, Weiss P, Farfel Z, Martinowitz U, Bank H. Eur J Clin Pharmacol 1985;28:257-261.",
"Steady-state interaction between amiodarone and phenytoin in normal subjects. [ PMID 2337037 ] Nolan PE, Erstad BL, Hoyer GL, Bliss M, Gear K, Marcus FI. Am J Cardiol 1990;65:1252-1257."
],
"fluconazole": [
"Effect of fluconazole on the disposition of phenytoin. [ PMID 2015731 ] Blum RA, Wilton JH, Hilligoss DM, Gardner MJ, Henry EU, Harrison NJ, Schentag JJ. Clin Pharmacol Ther 1991;49:420-425.",
"Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. [ PMID 8801056 ] Kunze KL, Wienkers LC, Thummel KE, Trager WF. Drug Metab Dispos. 1996 Apr;24(4):414-21.",
"Interaction of flurbiprofen with cranberry juice, grape juice, tea, and fluconazole: in vitro and clinical studies. [ PMID 16413247 ] Greenblatt DJ, von Moltke LL, Perloff ES, Luo Y, Harmatz JS, Zinny MA. Clin Pharmacol Ther. 2006 Jan;79(1):125-33.",
"Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174. [ PMID 9551703 ] Kaukonen KM, Olkkola KT, Neuvonen PJ. Eur J Clin Pharmacol. 1998 Feb;53(6):445-9."
],
"fluvastatin": [
"In vivo inhibition profile of cytochrome P450tb (CYP2C9) by (±)-fluvastatin. [ PMID 7586933 ] Transon C, Leemann T, Vogt N, Dayer P. Clin Pharmacol Ther 1995;58(4):412-417."
],
"fluvoxamine": [
"Inhibition of CYP2C9 by selective serotonin reuptake inhibitors: in vitro studies with tolbutamide and (S)-warfarin using human liver microsomes. [ PMID 10192756 ] Hemeryck A, De Vriendt C, Belpaire FM. Eur J Clin Pharmacol 1999 Feb;54(12):947-51."
],
"isoniazid": [
"Clinical importance of the interaction of phenytoin and isoniazid: a report of the Boston Collaborative Drug Surveillance Program. [ PMID 421578 ] Miller RR, Porter J, Greenblatt DJ. Chest 1979;75(3):356-358."
],
"lovastatin": [
"Warfarin Interaction. [ PMID 2241455 ] Ahmad S. Arch Int Med 1990;150:2407-2408."
],
"phenylbutazone": [
"Stereochemical aspects of warfarin drug interactions: Use of a combined pharmacokinetic- pharmacodynamic model. [ PMID 7924124 ] Chan E, McLachlan A, O'Reilly, Rowland M. Clin Pharmacol Ther 1994;56(3):286-294."
],
"probenicid": [
"Naproxen-probenecid interaction. [ PMID 710028 ] Runkel R, Mroszczak E, Chaplin M, Sevelius H, Segre E. Clin Pharmacol Ther 1978 Dec;24(6):706-713."
],
"sertraline": [
"Inhibition of CYP2C9 by selective serotonin reuptake inhibitors in vitro: studies of phenytoin p-hydroxylation. [ PMID 9384467 ] Schmider J, Greenblatt DJ, von Moltke LL, Karsov D, Shader RI. Br J Clin Pharmacol. 1997 Nov;44(5):495-8.",
"Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes. [ PMID 10510155 ] Xu ZH, Wang W, Zhao XJ, Huang SL, Zhu B, He N, Shu Y, Liu ZQ, Zhou HH. Br J Clin Pharmacol. 1999 Sep;48(3):416-23."
],
"sulfamethoxazole": [
"Formation and disposition of sulfamethoxazole hydroxylamine (SMX-MA). Spielberg SP, Nuss CE, Cribb AE. Clin Pharmacol Ther 1995;57(2):221 Abst."
],
"sulfaphenazole": [
"In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides, and quinolines. [ PMID 3203057 ] Back DJ, Tjia JF, Karbwang J, Colbert J. Br J Clin Pharmacol 1988;26:23-29."
],
"teniposide": [
"Tolbutamide and mephenytoin hydroxylation by human cytochrome P450s in the CYP2C subfamily. [ PMID 2299601 ] Relling MV, Aoyama T, Gonzalez FJ, Meyer UA. J Pharmacol Exp Ther 1990 Jan;252(1):442-7."
],
"ticlopidine": [
"Ticlopdine inhibition of phenytoin metabolism mediated by potent inhibition of CYP2C19. [ PMID 9390115 ] Donahue SR, Flockhart DA, Abernethy DR, Ko JW. Br Clin Pharmacol Ther 1997 Nov;62(5):572-7."
],
"trimethoprim": [
""
],
"voriconazole": [
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"Drug-drug interaction of antifungal drugs. [ PMID 16205037 ] Niwa T, Shiraga T, Takagi A. Yakugaku Zasshi. 2005 Oct;125(10):795-805."
],
"zarfirlukast": [
"(Accolate®) Prescriber's Letter 1996;3(10) 55. (October)"
]
}
},
"2b6": {
"substrates": {
"bupropion": [
"Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. [ PMID 10997944 ] Faucette SR, Hawke RL, Lecluyse EL, Shord SS, Yan B, Laethem RM, Lindley CM. Drug Metab Dispos 2000 Oct;28(10):1222-30"
],
"cyclophosphamide": [
"Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. [ PMID 8242617 ] Chang TK, Weber GF, Crespi CL, Waxman DJ Cancer Res 1993 Dec 1;53(23):5629-37."
],
"efavirenz": [
"Pharmacokinetics of efavirenz when co-administered with rifampin in TB/HIV co-infected patients: pharmacogenetic effect of CYP2B6 variation. [ PMID 18728241 ] Kwara A, Lartey M, Sagoe KW, Xexemeku F, Kenu E, Oliver-Commey J, Boima V, Sagoe A, Boamah I, Greenblatt DJ, Court MH. J Clin Pharmacol. 2008 Sep;48(9):1032-40.",
"High prevalence of the CYP2B6 516G-->T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe. [ PMID 18057928",
"] Nyakutira C, Röshammar D, Chigutsa E, Chonzi P, Ashton M, Nhachi C, Masimirembwa C. Eur J Clin Pharmacol. 2008 Apr;64(4):357-65."
],
"ifosphamide": [
"Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. [ PMID 8242617 ] Chang TK, Weber GF, Crespi CL, Waxman DJ Cancer Res 1993 Dec 1;53(23):5629-37.",
"Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes. [ PMID 10101149 ] Granvil CP, Madan A, Sharkawi M, Parkinson A, Wainer IW Drug Metab Dispos 1999 Apr;27(4):533-41."
],
"methadone": [
"Role of CYP2B6 in stereoselective human methadone metabolism. [ PMID 18292673 ] Totah RA, Sheffels P, Roberts T, Whittington D, Thummel K, Kharasch ED. Anesthesiology. 2008 Mar;108(3):363-74."
],
"sorafenib": [
"Prescribing Information"
]
},
"inducers": {
"phenobarbital": [
"Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: Response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. [ PMID 9157990 ] Chang TK, Yu L, Maurel P, Waxman DJ Cancer Res 1997 May 15;57(10):1946-54"
],
"phenytoin": [
"Phenytoin-induced alteration in the N-dechloroethylation of ifosfamide stereoisomers. [ PMID 9332469 ] Ducharme MP, Bernstein ML, Granvil CP, Gehrcke B, Wainer IW Cancer Res 1997 May 15;40(6):531-3"
]
},
"inhibitors": {
"thiotepa": [
"Triethylenethiophosphoramide is a specific inhibitor of cytochrome P450 2B6: Implications for cyclophosphamide metabolism. [ PMID 11950782 ] Rae JM, Soukhova NV, Flockhart DA, Desta Z. Drug Metab Dispos 2002;30(5)"
],
"ticlopidine": [
"Mechanism-based inhibition of human cytochrome P450 2B6 by ticlopidine, clopidogrel, and the thiolactone metabolite of prasugrel. [ PMID 19047469 ] Nishiya Y, Hagihara K, Ito T, Tajima M, Miura SI, Kurihara A, Farid NA, Ikeda T. Drug Metab Dispos. 2008 Dec 1."
]
}
}
}
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