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Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients

Abstract:

This study investigated to what extent fluvoxamine affects the pharmacokinetics of thioridazine (THD) in schizophrenic patients under steady-state conditions. Concentrations of THD, mesoridazine, and sulforidazine were measured in plasma samples obtained from 10 male inpatients, aged 36 to 78 years, at three different time points: A, during habitual monotherapy with THD at 88 ± 54 mg/day; B, after addition of a low dosage of fluvoxamine (25 mg twice a day) for 1 week; and C, 2 weeks after fluvoxamine discontinuation. After the addition of fluvoxamine, THD concentrations relative to time point A significantly increased approximately threefold from 0.40 to 1.21 μmol/L (225%) (p < 0.002), mesoridazine concentrations increased from 0.65 to 2.0 μmol/L (219%) (p < 0.004), and sulforidazine levels increased from 0.21 to 0.56 μmol/L (258%) (p < 0.004). The THD-mesoridazine 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 patients 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 CYPIA2 enzyme level. Therefore, clinicians should be aware of the potential for a clinical drug interaction between both compounds, and careful monitoring of THD levels is valuable to prevent the accumulation of the drug and resulting toxicity.