Effects of the CYP 2D6 Genotype and Cigarette Smoking on the Steady-State Plasma Concentrations of Fluvoxamine and Its Major Metabolite Fluvoxamino Acid in Japanese Depressed Patients

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Abstract
The effects of the cytochrome P450 (CYP) 2D6 genotype and cigarette smoking on the steady-state plasma concentrations (Css) of fluvoxamine (FLV) and its demethylated metabolite fluvoxamino acid (FLA) were studied in 49 Japanese depressed patients receiving FLV 200 mg/d. The Css of FLV and FLA were measured by HPLC, and the wild-type allele (*1) and two mutated alleles causing absent (*5) or decreased (*10) CYP 2D6 activity were identified by PCR methods. The patients were divided into three genotype groups by the number of mutated alleles: 12 cases with no (*1/*1), 27 cases with one (*1/*5 and *1/*10), and 10 cases with two (*5/*10 and *10/*10) mutated alleles. The means ± SD of the Css of FLV and FLA and the FLA/FLV ratio of all patients were 169.1 ± 147.5 ng/mL, 83.9 ± 52.7 ng/mL, and 0.71 ± 0.50, respectively. The Css of FLV and FLA were not significantly different among the three genotype groups. However, the FLA/FLV ratio was significantly lower in the patients with one (P P