title: Absorption, metabolism, and excretion of risperidone in humans.
abstract: The absorption, metabolism, and excretion of the novel antipsychotic risperidone was studied in three healthy male subjects. One week after a single oral dose of 1 mg [14C]risperidone, 70% of the administered radioactivity was recovered in the urine and 14% in the feces. Unchanged risperidone was mainly excreted in the urine and accounted for 30, 11, and 4% of the administered dose in the poor, intermediate, and extensive metabolizer of debrisoquine, respectively. Alicyclic hydroxylation at the 9-position of the tetrahydro-4H-pyrido[1,2-a]-pyrimidin-4-one moiety was the main metabolic pathway. The active metabolite 9-hydroxy-risperidone accounted for 8, 22, and 32% of the administered dose in the urine of the poor, intermediate, and extensive metabolizer, respectively. Oxidative N-dealkylation at the piperidine nitrogen, whether or not in combination with the 9-hydroxylation, accounted for 10-13% of the dose. In methanolic extracts of feces, risperidone, and benzisoxazole-opened risperidone and hydroxylated metabolites were detected. 9-Hydroxy-risperidone was by far the main plasma metabolite. The sum of risperidone and 9-hydroxy-risperidone accounted for the largest part of the plasma radioactivity in the three subjects. Although the debrisoquine-type genetic polymorphism plays a distinct role in the metabolism of risperidone, the pharmacokinetics of the active fraction (i.e. risperidone plus 9-hydroxy-risperidone) remained similar among the three subjects.
authors.affiliation: Department of Drug Metabolism and Pharmacokinetics, Janssen Research Foundation, Beerse, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Mannens
authors.forename: M L
authors.initials: ML
authors.lastname: Huang
authors.forename: W
authors.initials: W
authors.lastname: Meuldermans
authors.forename: J
authors.initials: J
authors.lastname: Hendrickx
authors.forename: R
authors.initials: R
authors.lastname: Woestenborghs
authors.forename: J
authors.initials: J
authors.lastname: Heykants
mesh_terms: D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D002250:Carbon Radioisotopes; D006801:Humans; D007408:Intestinal Absorption; D007555:Isoxazoles / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D010880:Piperidines / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D018967:Risperidone
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D007555:Isoxazoles; D010880:Piperidines; D018967:Risperidone