Effect of fluvoxamine on the pharmacokinetics of imipramine and desipramine in healthy subjects.
The effect of the selective serotonin reuptake inhibitor fluvoxamine (100 mg/day for 10 consecutive days) on the kinetics of a single oral dose of imipramine (50 mg) and desipramine (100 mg) was investigated in 12 healthy subjects. Compared with a control session, treatment with fluvoxamine caused a significant prolongation of imipramine half-life (from 22.8 +/- 6.4 to 40.5 +/- 5.0 h, means +/- SD, p < 0.01) and a marked decrease in imipramine apparent oral clearance (from 1.02 +/- 0.19 to 0.28 +/- 0.06 L/h/kg, p < 0.0001). No significant changes in desipramine kinetics were observed during fluvoxamine treatment. These findings indicate that, at the dosage tested, fluvoxamine markedly inhibits the demethylation of imipramine without affecting significantly the CYP2D6-mediated hydroxylation of desipramine.
Spina
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Institute of Pharmacology, University of Messina, Italy.
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AP
D000328:Adult; D003891:Desipramine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D016666:Fluvoxamine / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007099:Imipramine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
D016666:Fluvoxamine; D007099:Imipramine; D003891:Desipramine