Clovoxamine kinetics in an early clinical trial

Elimination kinetics of the new antidepressant clovoxamine were determined in a preliminary clinical trial in 10 depressed patients. When final oral doses of 50 mg clovoxamine fumarate were given, the mean peak steady-state plasma concentration was about 60 ng/ml after 3 hr. Clovoxamine elimination proceeded by an apparent single-phasic, first-order decline with a mean t1/2 of 9.5 +/- 2.8 hr. One subject had an unusually long t1/2 (31.5 hr) and had correspondingly high clovoxamine plasma concentrations. The mean apparent volume of distribution (Vd) calculated from oral dosage was 19.5 +/- 6 l/kg, but one atypical subject had an apparent Vd of 96 l/kg. The mean apparent oral clearance was 25.5 +/- 12.5 ml/min/kg. These parameters should be of assistance in planning dosage regimens and monitoring therapeutic blood levels according to kinetic principles. Atypical clovoxamine kinetics can be associated with abnormally high or low blood levels and could therefore lead to variability in clinical response.