Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2.

Cytochrome P450 1A2 (CYP1A2) accounts for about 10 to 15% of the total CYP content of human liver and is the major enzyme involved in the metabolism of imipramine, propranolol, clozapine, theophylline, and caffeine. It is also involved in the conversion of heterocyclic amines to their proximal carcinogenic and mutagenic forms, as well as in the metabolism of endogenous substances, including 17 beta-estradiol and uroporphyrinogen III. Fluvoxamine is a potent inhibitor of CYP1A2, and there is potential for interaction with drugs that are metabolised by this isoenzyme. This property of fluvoxamine may be usefully applied to identifying agents that are substrates of CYP1A2, and it has a possible therapeutic application in the prevention of CYP1A2-mediated toxic metabolite formation.