Metabolism of drugs by cytochrome P450 3A isoforms. Implications for drug interactions in psychopharmacology.

Article Details

Citation
Copy to clipboard

von Moltke LL, Greenblatt DJ, Schmider J, Harmatz JS, Shader RI

Metabolism of drugs by cytochrome P450 3A isoforms. Implications for drug interactions in psychopharmacology.

Clin Pharmacokinet. 1995;29 Suppl 1:33-43; discussion 43-4.

PubMed ID
8846621 [ View in PubMed
]
Abstract

Members of the P450 3A subfamily are the most abundant of the human hepatic cytochromes. CYP3A isoforms mediate the biotransformation of many drugs, including a number of psychotropic, cardiac, analgesic, hormonal, immunosuppressant, antineoplastic, and antihistaminic agents. Activity of CYP3A in humans is variable among individuals, but there is no evidence of genetic polymorphism. Significant amounts of CYP3A are present in the gastrointestinal tract, and may contribute to presystemic extraction of drugs such as cyclosporin. The azole antifungal agents ketoconazole and itraconazole are potent inhibitors of human CYP3A isoforms. Selective serotonin reuptake inhibitor (SSRI) antidepressants are also CYP3A inhibitors, but much less potent than ketoconazole or itraconazole. In vitro models can provide important information on the qualitative and quantitative activity of potential inhibitors of human cytochromes. However, in vitro inhibition constant (Ki) values alone do not predict the magnitude of an in vivo interaction, nor whether an interaction will be of clinical importance. For example, SSRIs are predicted to impair clearance of the antihistamine terfenadine in humans. However, the magnitude of this effect is much less than would be associated with a pharmacokinetic interaction of clinical importance.

DrugBank Data that Cites this Article

Drugs