title: Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application.
abstract: Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t1/2 beta), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g t1/2 beta values were 5.5 and 4.7 h, respectively, mean-g tmax data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g Cmax maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag, tmax, and Cmax. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite "reduced benperidol" were found to be very low.
authors.affiliation: Department of Psychiatry, University of Mainz, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Seiler
authors.forename: H
authors.initials: H
authors.lastname: Wetzel
authors.forename: A
authors.initials: A
authors.lastname: Hillert
authors.forename: G
authors.initials: G
authors.lastname: Schöllnhammer
authors.forename: M
authors.initials: M
authors.lastname: Langer
authors.forename: U
authors.initials: U
authors.lastname: Barlage
authors.forename: C
authors.initials: C
authors.lastname: Hiemke
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001544:Benperidol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D001544:Benperidol