Pharmacokinetics of chlorprothixene after single intravenous and oral administration of three galenic preparations.
The absolute and relative bioavailability of chlorprothixene (CAS 113-59-7, Truxal) was studied in eight healthy male volunteers with three 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-block design with washout periods of two weeks. Serum concentrations of chlorprothixene were assayed using a high-performance liquid chromatographic method with electrochemical detection. After a 1-h infusion period the maximum serum concentration (Cmax) of chlorprothixene was 430 +/- 81 ng/ml (mean +/- S.D.) and subsequently decreased with a terminal elimination half-life (t1/2) of 25.8 +/- 13.6 h. The total serum clearance (Cl) and the apparent volume of distribution at steady state (Vss) were 867 +/- 167 ml/min and 1035 +/- 356 l, respectively. The profiles of the chlorprothixene serum concentration vs. time and the resulting pharmacokinetic parameters were similar for all orally administered formulations. The absolute oral bioavailability of 17% of the solution indicated a marked presystemic metabolism. The bioavailability of chlorprothixene relative to the oral solution was 56.4% with the coated tablet and 67.7% with the suspension. All pharmacokinetic parameters showed wide inter-subject variations, partly attributable to the respective formulation.
Bagli
M
M
Psychiatrische Klinik und Poliklinik, Rheinischen Friedrich-Wilhelms-Universität, Bonn, Germany.
Rao
M L
ML
Höflich
G
G
Kasper
S
S
Langer
M
M
Barlage
U
U
Beneke
M
M
Süverkrüp
R
R
Möller
H J
HJ
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D002749:Chlorprothixene / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013535:Suspensions; D013608:Tablets, Enteric-Coated
D014150:Antipsychotic Agents; D013535:Suspensions; D013608:Tablets, Enteric-Coated; D002749:Chlorprothixene