Antidepressant drug interactions and the cytochrome P450 system: a critical appraisal.
Evaluation of the inhibitory effects of antidepressant drugs on hepatic cytochrome P450 isoenzymes can allow clinicians to predict drug interactions occurring via this mechanism a priori. The magnitude and clinical relevance of these drug interactions are dependent on many factors including concentration of the isoenzyme inhibitor, contribution of active metabolites with isoenzyme inhibitory activity, and toxicity of the concomitant medication. This review summarizes information to date regarding the inhibitory potency of fluoxetine, fluvoxamine, paroxetine, sertraline, nefazodone, and venlafaxine on five isoenzyme systems: CYP2D6, CYP3A3/4, CYP1A2, CYP2C9, and CYP2C19. Both in vitro and in vivo isoenzyme inhibition data are presented and correlated to drug interactions of clinical relevance.
Riesenman
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Department of Clinical Pharmacy, University of Texas Health Science Center at San Antonio 78284-6220, USA.
D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects*; D004347:Drug Interactions; D005473:Fluoxetine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006801:Humans; D006899:Mixed Function Oxygenases / Q000187:drug effects; D010088:Oxidoreductases / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology; D020280:Sertraline; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000187:drug effects
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D017374:Paroxetine; D003577:Cytochrome P-450 Enzyme System; D015057:1-Naphthylamine; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D039181:Steroid 16-alpha-Hydroxylase; D016666:Fluvoxamine; D020280:Sertraline