Clinical pharmacology and therapeutics
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Clin. Pharmacol. Ther. · Mar 2002
Clinical TrialLow daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19).
Fluvoxamine is metabolized by the polymorphic cytochrome P450 (CYP) 2D6 and the smoking-inducible CYP1A2. Therapeutic doses of fluvoxamine inhibit both CYP1A2 and CYP2C19. In this study we used extensive metabolizers (EMs) and poor metabolizers (PMs) of debrisoquin (INN, debrisoquine) (CYP2D6) and two probes, caffeine (CYP1A2) and omeprazole (CYP2C19), to investigate whether nontherapeutic doses of fluvoxamine inhibit CYP1A2 but possibly not CYP2C19. ⋯ No convincing evidence was found that CYP2D6 is an important enzyme for the disposition of fluvoxamine. Other factors seem to be more important. A nontherapeutic oral daily dose of fluvoxamine is sufficient to provide a marked inhibition of both caffeine (CYP1A2) and omeprazole (CYP2C19) metabolism. It was not possible to separate the inhibitory effects of fluvoxamine on these enzymes, even after such a low daily dose such as 10 mg x 1 or x 2 of fluvoxamine.