Absorption, metabolism, and excretion of risperidone in humans

Drug Metab Dispos. 1993 Nov-Dec;21(6):1134-41.


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.

MeSH terms

  • 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


  • Antipsychotic Agents
  • Carbon Radioisotopes
  • Isoxazoles
  • Piperidines
  • Risperidone