SCHOOL OF MEDICINE

Department of Medicine

Clinical Pharmacology

3A457 REFERENCES

 3A4,5,7 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.

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

 


 3A4,5,7 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.


 3A4,5,7 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.

TROGLITAZONE