Nonlinear Pharmacokinetics of Fluvoxamine and Gender Differences

This prospective study assessed fluvoxamine serum concentrations under two different fixed doses. The study included 15 male and female patients who met the DSM-III-R criteria for major depression. They were prescribed 50 mg fluvoxamine twice a day for 2 weeks and 100 mg twice a day thereafter. Drug monitoring was carried out on days 14 and 28. Fluvoxamine serum concentrations were highly variable between patients. After the dose was doubled, the serum concentrations of fluvoxamine increased disproportionately (mean, 3.4-fold), and there was a significantly (p < 0.05) more pronounced increase in men (4.6-fold) than in women (2.4-fold). These results provide evidence of nonlinear, sex-dependent pharmacokinetics of fluvoxamine.