Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients

This study investigated to what extent fluvoxamine affects thioridazine (TH D) under steady-state conditions. Concentrations of THD, mesoridazine, and sulforidazine were measured in plasma samples obtained from 10 male inpatie nts, aged 36 to 78 years, at three different time points: A, during habitua l monotherapy with THD at 88 +/- 54 mg/day; B, after addition of a low dosa ge of fluvoxamine (25 mg twice a day) for 1 week; and C, 2 weeks after fluv oxamine discontinuation. After the addition of fluvoxamine, THD concentrati ons relative to time point A significantly increased approximately threefol d from 0.40 to 1.21 mu mol/L (225%) (p < 0.002), mesoridazine concentration s increased from 0.65 to 2.0 mu mol/L (219%) (p < 0.004), and sulforidazine levels increased from 0.21 to 0.56 mu mol/L (258%) (p < 0.004). The THD-me soridazine and THD-sulforidazine ratios remained unchanged during the study . Mean plasma THD, mesoridazine, and sulforidazine levels decreased at time point C, but despite fluvoxamine discontinuation for 2 weeks, three patien ts continued to exhibit elevated concentrations of THD and its metabolites. In conclusion, fluvoxamine markedly interferes with the metabolism of THD, probably at the CYP2C19 and/or CYP1A2 enzyme level. Therefore, clinicians should be aware of the potential for a clinical drug interaction between bo th compounds, and careful monitoring of THD levels is valuable to prevent t he accumulation of the drug and resulting toxicity.