Absorption, metabolism, and excretion of risperidone in humans

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 ma...

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Bibliographic Details
Published inDrug metabolism and disposition Vol. 21; no. 6; p. 1134
Main Authors Mannens, G, Huang, M L, Meuldermans, W, Hendrickx, J, Woestenborghs, R, Heykants, J
Format Journal Article
LanguageEnglish
Published United States 01.11.1993
Subjects
Administration, Oral
Adult
Antipsychotic Agents - metabolism
Antipsychotic Agents - pharmacokinetics
Antipsychotic Agents - urine
Carbon Radioisotopes
Humans
Intestinal Absorption
Isoxazoles - metabolism
Isoxazoles - pharmacokinetics
Isoxazoles - urine
Male
Piperidines - metabolism
Piperidines - pharmacokinetics
Piperidines - urine
Risperidone
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Summary: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.
ISSN:0090-9556