PHARMACOKINETICS AND BIOAVAILABILITY OF BENPERIDOL IN SCHIZOPHRENIC-PATIENTS AFTER INTRAVENOUS AND 2 DIFFERENT KINDS OF ORAL APPLICATION

Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperido l as an intravenous (i.v.) bolus injection, orally as liquid, and oral ly as tablets using a partially randomized cross-over design. Drug pla sma levels were determined by high performance liquid chromatography w ith electrochemical detection and subjected to model independent pharm acokinetic analyses. After i.v. dosing the geometric means (mean-g) we re 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t(1/2 beta)), 4.21 1/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 1/(h()kg) for the cleara nce. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentr ations were 0.33 and 1.1 h, mean-g t(1/2 beta) values were 5.5 and 4.7 h, respectively, mean-g t(max) data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g C-max (max)values were 10.2 an d 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag, t(max), and C-max. Mean-g abs olute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhib ited large intersubject variation. The plasma concentrations of the pr esumed metabolite ''reduced benperidol'' were found to be very low.