title: Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects.
abstract: The pharmacokinetics of a novel antipsychotic agent, risperidone, and the prolactin response were studied in 12 dextromethorphan-phenotyped healthy men after administration of 1 mg risperidone intravenously, intramuscularly, and orally. The formation of the equipotent major metabolite, 9-hydroxyrisperidone, exhibited CYP2D6-related polymorphism. The plasma area under the concentration-time curve from time zero to infinity ratio of 9-hydroxyrisperidone to risperidone averaged 3 (intravenous and intramuscular) and 6 (oral administration) in the extensive metabolizers and 0.2 in the poor metabolizers. Risperidone half-life was about 3 hours in extensive metabolizers and 22 hours in poor metabolizers. Risperidone absolute oral bioavailability was 66%. The pharmacokinetics of the active moiety (risperidone plus 9-hydroxyrisperidone) varied little among subjects (mean terminal half-life, 20 +/- 2 1/2 hours; absolute oral and intramuscular bioavailability, 100%). The prolactin response correlated best with the plasma active moiety, which showed little hysteresis. It is concluded that risperidone metabolic polymorphism on increased plasma prolactin is minimal and that the active moiety is clinically relevant.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Janssen Research Foundation, Beerse, Belgium.
authors.forename: M L
authors.initials: ML
authors.lastname: Huang
authors.forename: A
authors.initials: A
authors.lastname: Van Peer
authors.forename: R
authors.initials: R
authors.lastname: Woestenborghs
authors.forename: R
authors.initials: R
authors.lastname: De Coster
authors.forename: J
authors.initials: J
authors.lastname: Heykants
authors.forename: A A
authors.initials: AA
authors.lastname: Jansen
authors.forename: Z
authors.initials: Z
authors.lastname: Zylicz
authors.forename: H W
authors.initials: HW
authors.lastname: Visscher
authors.forename: J H
authors.initials: JH
authors.lastname: Jonkman
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001682:Biological Availability; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011388:Prolactin / Q000097:blood / Q000187:drug effects*; D011897:Random Allocation; D012016:Reference Values; D018967:Risperidone
chemical_list: D014150:Antipsychotic Agents; D007555:Isoxazoles; D010880:Piperidines; D011388:Prolactin; D018967:Risperidone