Inhibition of Trazodone Metabolism by Thioridazine in Humans

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Abstract
To clarify the involvement of cytochrome P4502D6 (CYP2D6) in the metabolism of trazodone, the effects of coadministration of thioridazine, which is an inhibitor of this isozyme, on plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine (m-CPP) were studied. The subjects were 11 depressed patients receiving trazodone at bedtime for 1–18 weeks. The dose was 150 mg in 10 patients and 300 mg in one. Thioridazine 40 mg/day was coadministered for 1 week, and blood samplings were performed before and after the coadministration. Thioridazine significantly (p < 0.001) increased plasma concentrations of both trazodone (713 ± 252 vs. 969 ± 370 ng/ml) and m-CPP (61 ± 22 vs. 94 ± 34 ng/ml). The present study thus suggests that CYP2D6 is involved in the metabolism of trazodone.

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