title: Pharmacokinetic study of iminodibenzyl antipsychotic drugs, clocapramine and Y-516 in dog and man.
abstract: The pharmacokinetic properties of the iminodibenzyl antipsychotic drugs clocapramine (CCP, 3-chloro-5-[3-(4-carbamoyl-4-piperidino piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) and Y-516 (3-chloro-5-[3-(2-oxo-1, 2, 3, 5, 6, 7, 8, 8a-octahydroimidazo [1,2-a] pyridine-3-spiro-4'-piperidino) propyl]-10, 11-dihydro-5H-dibenzo[b, f]azepine) were investigated in dog and man. Dogs were administered CCP and Y-516 intravenously, intraperitoneally, and orally, and the concentrations of the parent drugs and their metabolites in the plasma and urine were determined. Half-life (t1/2) was approximately the same by all three administration routes, being approximately 5 h for CCP and 3 h for Y-516. Bioavailability following oral administration was 0.16 +/- 0.01 (mean +/- SD, n = 3) for CCP and 0.29 +/- 0.07 for Y-516. The fractions of dose absorbed following oral administration were 0.43 +/- 0.07 and 0.79 +/- 0.24, and the fractions of dose metabolized in the liver due to the first-pass effect were 0.63 +/- 0.05 and 0.63 +/- 0.04 for CCP and Y-516, respectively. Y-516 was detected in the plasma after intraperitoneal and oral administration of CCP. The ratio of the AUC of Y-516 to that of CCP was 0.06 following intraperitoneal administration and 0.40 following oral administration. This indicated that while the metabolism of CCP into Y-516 may occur partly in the liver due to the first-pass effect, it occurs mostly within the gastrointestinal tract itself or its mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Psychiatry, Kitasato University School of Medicine, Kanagawa, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Ishigooka
authors.forename: M
authors.initials: M
authors.lastname: Murasaki
authors.forename: H
authors.initials: H
authors.lastname: Wakatabe
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: K
authors.initials: K
authors.lastname: Hikida
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Nobunaga
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000652:urine; D001552:Benzazepines / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003984:Dibenzazepines / Q000493:pharmacokinetics* / Q000652:urine; D004285:Dogs; D006801:Humans; D008297:Male; D013045:Species Specificity; D014149:Tranquilizing Agents / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D014150:Antipsychotic Agents; D001552:Benzazepines; D003984:Dibenzazepines; D014149:Tranquilizing Agents; C046384:mosapramine; C000449:3-chlorocarpipramine