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 d ose 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 ma rked decrease in imipramine apparent oral clearance (from 1.02 +/- 0.1 9 to 0.28 +/- 0.06 L/h/kg, p < 0.0001). No significant changes in desi pramine kinetics were observed during fluvoxamine treatment. These fin dings indicate that, at the dosage tested, fluvoxamine markedly inhibi ts the demethylation of imipramine without affecting significantly the CYP2D6-mediated hydroxylation of desipramine.