Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients.
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 micromol/L (225%) (p < 0.002), mesoridazine concentrations increased from 0.65 to 2.0 micromol/L (219%) (p < 0.004), and sulforidazine levels increased from 0.21 to 0.56 micromol/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 CYP1A2 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.
Carrillo
J A
JA
Department of Pharmacology and Psychiatry, Medical School, University of Extremadura, Badajoz, Spain.
Ramos
S I
SI
Herraiz
A G
AG
Llerena
A
A
Agundez
J A
JA
Berecz
R
R
Duran
M
M
Benítez
J
J
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D004347:Drug Interactions; D016666:Fluvoxamine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008653:Mesoridazine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013881:Thioridazine / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D014150:Antipsychotic Agents; D019389:Cytochrome P-450 CYP2D6; D016666:Fluvoxamine; D008653:Mesoridazine; D017367:Selective Serotonin Reuptake Inhibitors; D013881:Thioridazine