PHARMACOKINETICS OF CHLORPROTHIXENE AFTER SINGLE INTRAVENOUS AND ORAL-ADMINISTRATION OF 3 GALENIC PREPARATIONS

The absolute and relative bioavailability of chlorprothixene (CAS 113- 59-7, Truxal(R)) was studied in eight healthy male volunteers with thr ee different formulations: solution, suspension and coated tablet. An intravenous infusion and an oral aqueous solution served as references . Single doses of 100 mg were administered in a randomized complete-bl ock design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatog raphic method with electrochemical detection. After a 1-h infusion per iod the maximum serum concentration (C-max) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a termin al elimination half-life (t(1/2)) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady slate (V-ss) were 867 +/- 167 ml/min and 1035 +/- 3561, respectively. The p rofiles of the chlorprothixene serum concentration vs. time and the re sulting pharmacokinetic parameters were similar for all orally adminis tered formulations. The absolute oral bioavailability of 17% of the so lution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the co ated tablet and 67.7% with the suspension. All pharmacokinetic paramet ers showed wide inter-subject variations, partly attributable to the r espective formulation.