Psychopharmacology: Cytochrome P450 Substrates, Inhibitors and Inducers

PubMed Reference Sheet (with links)

amitriptyline:

Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4.
Venkatakrishnan K, Greenblatt DJ, et al.
 J Clin Pharmacol. 1998 Feb;38(2):112-21

Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes.
Olesen OV, Linnet K.
Pharmacology. 1997 Nov;55(5):235-43.

aripiprazole: PubMed

Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder.
Swainston Harrison T, Perry CM.
Drugs. 2004;64(15):1715-36

bupropion: PubMed

Inhibition of CYP2D6 Activity by Bupropion.
Kotlyar M, Brauer LH, Tracy TS, Hatsukami DK, Harris J, Bronars CA, Adson DE
J Clin Psychopharmacol. 2005 Jun;25(3):226-229

Bupropion: pharmacology and therapeutic applications.
Foley KF, DeSanty KP, Kast RE.
Expert Rev Neurother. 2006 Sep;6(9):1249-65

caffeine:

Determination of urinary metabolites of caffeine for the assessment of cytochrome P4501A2, xanthine oxidase, and N-acetyltransferase activity in humans.
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.
Tang BK, Kalow W
Methods Enzymol 1996;272:124-131

carbamazepine:

Clinically significant pharmacokinetic drug interactions with carbamazepine. An update.
Spina E, Pisani F, Perucca E.
Clin Pharmacokinet. 1996 Sep;31(3):198-214

citalopram

Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA-expressed cytochrome P450 enzymes.
Olesen OV, Linnet K.
Pharmacology. 1999 Dec;59(6):298-309

clomipramine:

The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways.
Nielsen KK, Flinois JP, Beaune P, Brøsen K.
J Pharmacol Exp Ther. 1996 Jun;277(3):1659-64

clopidogrel

Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation.
Turpeinen M, Tolonen A, et al.
Clin Pharmacol Ther. 2005 Jun;77(6):553-9

clozapine: PubMed

Metabolism and bioactivation of clozapine by human liver in vitro. Pirmohamed, M., Williams, D., Madden, S., Templeton, E., and Park, B.K.
J Pharmacol Exp Ther 272(3):984-990, 1995

Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test.
Bertilsson, L., Carrillo, J.A., Dahl, M.-L., Llerena, A., Alm, C., Bondesson, U., Lindstrom, L., de la Rubia, I.R., Ramos, S., and Benitez, J
Br J Clin Pharmacol 38:471-473, 1994

diazepam:

Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19 and the 3A subfamily.
Ono S, Hatanaka T, Miyazawa S, Tsutsui M, Aoyama T, Gonzalez FJ, Satoh T.
Xenobiotica. 1996 Nov;26(11):1155-66

duloxetine: PubMed

Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers.
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

In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine.
Lobo ED, Bergstrom RF, Reddy S, Quinlan T, Chappell J, Hong Q, Ring B, Knadler MP.
Clin Pharmacokinet. 2008;47(3):191-202.

fluoxetine: PubMed

Fluoxetine metabolism and pharmacological interactions: the role of cytochrome p450.
Mandrioli R, Forti GC, Raggi MA.
Curr Drug Metab. 2006 Feb;7(2):127-33

Fluoxetine inhibits the metabolism of tolterodine-pharmacokinetic implications and proposed clinical relevance.
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.
Hara Y, Nakajima M, Miyamoto KI, Yokoi T.
Xenobiotica. 2005 Jun;35(6):549-60

fluvoxamine: PubMed

Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity.
Carillo JA, Dahl M-L, Svennson J-O, Alm C, Rodriguez I, Bertillson L
Clin Pharmacol Ther 1996;60:183-190

grapefruit

Interaction between grapefruit juice and diazepam in humans.
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.
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.
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.
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.
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

haloperidol:

Pharmacokinetics of haloperidol: an update.
Kudo S, Ishizaki T.
Clin Pharmacokinet. 1999 Dec;37(6):435-56

imipramine: PubMed

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.
Koyama E, Chiba K, Tani M, Ishizaki T
J Pharmacol Exp Ther 1997 Jun;281(3):1199-1210

methadone:

Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone.
Kharasch ED, Hoffer C, Whittington D, Sheffels P.
Clin Pharmacol Ther. 2004 Sep;76(3):250-69

mirtazapine:

Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression.
Fawcett J, Barkin RL.
J Affect Disord. 1998 Dec;51(3):267-85.

modafinil: PubMed

In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil.
Robertson P, DeCory HH, Madan A, Parkinson A.
Drug Metab Dispos 2000 Jun;28(6):664-71

nefazodone

Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers.
DeVane CL, Donovan JL, et al.
J Clin Psychopharmacol. 2004 Feb;24(1):4-10

Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole.
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.
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.
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.
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.
Barbhaiya RH, Shukla UA, Kroboth PD, Greene DS.
J Clin Psychopharmacol. 1995 Oct;15(5):320-6

oral contraception

Pharmacokinetic drug interactions involving 17 alpha-ethinylestradiol: a new look at an old drug.
Zhang H, Cui D, Wang B, Han YH, Balimane P, Yang Z, Sinz M, Rodrigues AD.
Clin Pharmacokinet. 2007;46(2):133-57

olanzapine: PubMed

Olanzapine. Pharmacokinetic and pharmacodynamic profile. Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM.
Clin Pharmacokinet. 1999 Sep;37(3):177-93

paroxetine:

Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine.
Jeppesen U, Gram LF, et al.
Eur J Clin Pharmacol. 1996;51(1):73-8

proton pump inhibitors

Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump inhibitor.
VandenBranden M, Ring BJ, Binkley SN, Wrighton SA.
Pharmacogenetics. 1996 Feb;6(1):81-91

Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.
Li XQ, Andersson TB, Ahlström M, Weidolf L. DMPK and Bioanalytical Chemistry, AstraZeneca R and D Mölndal, S-431 83 Mölndal, Sweden.
Drug Metab Dispos. 2004 Aug;32(8):821-7

quetiapine: PubMed

EEffects of cytochrome P450 3A modulators ketoconazole and carbamazepine on quetiapine pharmacokinetics.
Grimm SW, Richtand NM, Winter HR, Stams KR, Reele SB.
Br J Clin Pharmacol. 2006 Jan;61(1):58-69

Metabolic mechanism of quetiapine in vivo with clinical therapeutic dose.
Li KY, Li X, Cheng ZN, Li HD.
Methods Find Exp Clin Pharmacol. 2005 Mar;27(2):83-6

ropinirole:

Clinical pharmacokinetics of ropinirole.
Kaye CM, Nicholls B.
Clin Pharmacokinet. 2000 Oct;39(4):243-54.

selegiline:

CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson's disease, as revealed from experiments with recombinant enzymes.
Hidestrand M, Oscarson M, et al.
Drug Metab Dispos. 2001 Nov;29(11):1480-4

sertraline: PubMed

The effect of sertraline on the pharmacokinetics of desipramine and imipramine.
Kurtz DL, Bergstrom RF, Goldberg MJ, Cerimele BJ.
Clin Pharmacol Ther. 1997 Aug;62(2):145-56

ticlopidine

Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation.
Turpeinen M, Tolonen A, et al.
Clin Pharmacol Ther. 2005 Jun;77(6):553-9

tobacco: PubMed

Effect of smoking on caffeine clearance.
PParsons WD, Neims AH
Clin pharmacol Ther 1978;24(1):40-45

Assessment of the cytochrome P-448 dependent liver enzyme system by a caffeine breath test.
Wietholz H, Voegelin M, Arnaud MJ, Bircher J, Preisig R
Eur J Clin Pharmacol 1981;21:53-59

topiramate: PubMed

Dose-dependent induction of cytochrome P450 (CYP) 3A4 and activation of pregnane X receptor by topiramate.
Nallani SC, Glauser TA, et al.
Epilepsia. 2003 Dec;44(12):1521-8