Clinical Pharmacokinetics of Dothiepin: Single-dose Kinetics in Patients and Prediction of Steady-state Concentrations

Abstract

The pharmacokinetics of dothiepin were evaluated in 9 depressed patients following a single oral dose of 75mg. Blood and plasma concentrations of dothiepin and 2 major metabolites, northiaden and dothiepin S-oxide, were measured by gas chromatography/mass fragmentography. The mean (±SD) peak plasma concentrations of dothiepin were 49 ±27 μg/L at 3 ± l.2h. Mean (± SD) estimates of other parameters were as follows: absorption half-life 1.1 ± 1.1h; distribution half-life 2.2 ± 0.8h; elimination half-life 25 ± 7h; apparent volume of distribution 70 ± 62 L/kg; and oral clearance 2.1 ± 1.6 L/kg/h. The mean (±SD) peak plasma concentration of dothiepin S-oxide was 125 ± 43 μg/L at 3.5 ± 1.3h with an..