Serotonin selective reuptake inhibitor drug interactions and the cytochrome P450 system.
The article focuses on the effects of the serotonin selective reuptake inhibitors (SSRIs) on specific drug metabolizing isoenzymes: CYP2D6, CYP3A3/4, CYP1A2, CYP2C9, and CYP2C19. Both in vitro and in vivo data regarding the inhibition potential of the SSRIs at each of these isoenzyme systems are reviewed. In general, the magnitude of the in vivo interactions between the SSRIs and substrates for these isoenzyme systems mirrors to a large extent their in vitro inhibitory potencies. However, in vitro work is limited owing to pharmacokinetic considerations, the effect of metabolites on the isoenzymes, and the likelihood that several isoenzymes are co-responsible for the metabolism of a substrate.
Ereshefsky
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L
Clinical Pharmacy Programs, University of Texas Health Science Center, San Antonio State Hospital, USA.
Riesenman
C
C
Lam
Y W
YW
D000928:Antidepressive Agents / Q000378:metabolism / Q000493:pharmacokinetics / 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; D065607:Cytochrome P-450 Enzyme Inhibitors; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010599:Pharmacokinetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors
D000928:Antidepressive Agents; D001189:Aryl Hydrocarbon Hydroxylases; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6; D065607:Cytochrome P-450 Enzyme Inhibitors; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D004364:Pharmaceutical Preparations; D017367:Selective Serotonin Reuptake Inhibitors; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; C504573:CYP1A2 protein, human; C045793:CYP2C19 protein, human