What is the half-life of Risperidone (atypical antipsychotic)?

Half-Life of Risperidone

The half-life of risperidone is approximately 3 hours in extensive metabolizers and 20 hours in poor metabolizers, while its active metabolite 9-hydroxyrisperidone has a half-life of about 21 hours in extensive metabolizers and 30 hours in poor metabolizers, resulting in a combined active moiety half-life of approximately 20-23 hours. 1, 2

Pharmacokinetic Profile

• Risperidone is metabolized primarily by CYP2D6 to its active metabolite 9-hydroxyrisperidone (also known as paliperidone) 1
• The clinical effect of risperidone results from the combined concentrations of both risperidone and 9-hydroxyrisperidone 1
• Peak plasma concentrations are reached approximately 1-2 hours after oral administration 2
• The combined active moiety (risperidone plus 9-hydroxyrisperidone) has a terminal elimination half-life of approximately 20-23 hours 1, 2

Metabolizer Status Impact

• CYP2D6 enzyme is subject to genetic polymorphism, with approximately 6-8% of Caucasians and a very low percentage of Asians being poor metabolizers 1
• In extensive metabolizers (normal CYP2D6 function):
  • Risperidone half-life: approximately 3 hours 1
  • 9-hydroxyrisperidone half-life: approximately 21 hours 1
• In poor metabolizers (reduced CYP2D6 function):
  • Risperidone half-life: approximately 20 hours 1
  • 9-hydroxyrisperidone half-life: approximately 30 hours 1

Clinical Implications

• The long half-life of the combined active moiety (20-23 hours) allows for once or twice daily dosing regimens 2
• Despite differences in metabolizer status, the pharmacokinetics of the combined active moiety (risperidone plus 9-hydroxyrisperidone) are similar between extensive and poor metabolizers 1
• Dosing adjustments may be necessary in elderly patients as renal clearance of both risperidone and 9-hydroxyrisperidone is decreased, and elimination half-lives are prolonged compared to younger subjects 1

Drug Interactions

• CYP2D6 inhibitors (e.g., quinidine) can interfere with the conversion of risperidone to 9-hydroxyrisperidone, essentially giving all recipients a pharmacokinetic profile typical of poor metabolizers 1
• Enzyme inducers (e.g., carbamazepine, phenytoin, rifampin, phenobarbital) may decrease the combined plasma concentrations of risperidone and 9-hydroxyrisperidone 1
• Risperidone is a relatively weak inhibitor of CYP2D6 and is not expected to substantially affect the clearance of other drugs metabolized by this pathway 1

Special Considerations

• Renal excretion is the major route of elimination for risperidone and its metabolites, with approximately 70% of a dose excreted in urine 1
• Paliperidone (9-hydroxyrisperidone), available as a separate medication, has a half-life of approximately 23 hours 3, 4
• Dosing adjustments may be necessary in patients with renal or hepatic impairment 1