Half-Life of Risperdal (Risperidone)
The half-life of risperidone is approximately 3 hours in extensive metabolizers and 20 hours in poor metabolizers, but the clinically relevant active moiety (risperidone plus its equipotent metabolite 9-hydroxyrisperidone) has an overall mean elimination half-life of approximately 20-23 hours, allowing for once or twice-daily dosing. 1
Pharmacokinetic Details by Metabolizer Status
The half-life of risperidone varies significantly based on CYP2D6 metabolizer status:
- Extensive metabolizers (most patients): Risperidone half-life is approximately 3 hours (CV=30%), while 9-hydroxyrisperidone half-life is approximately 21 hours (CV=20%) 1
- Poor metabolizers (6-8% of Caucasians, very low percentage of Asians): Risperidone half-life extends to approximately 20 hours (CV=40%), while 9-hydroxyrisperidone half-life is approximately 30 hours (CV=25%) 1
Clinical Significance of the Active Moiety
The combined half-life of the active moiety (risperidone plus 9-hydroxyrisperidone) is what matters clinically, averaging 20-23 hours across all metabolizer types. 1, 2
This is critical because:
- 9-hydroxyrisperidone has similar pharmacological activity to the parent compound 1, 3
- The clinical effect results from combined concentrations of both compounds 1
- The pharmacokinetics of the combined active moiety are similar in extensive and poor metabolizers after single and multiple doses 1, 4
Dosing Implications
The 20-23 hour half-life of the active moiety supports:
- Twice-daily or once-daily dosing schedules 2
- Steady-state achievement in approximately 5-7 days (approximately 5 half-lives) 5
- When switching from risperidone, cross-titration should account for this half-life 6
Special Population Considerations
In elderly patients, elimination half-lives are prolonged compared to young healthy subjects due to decreased renal clearance of both risperidone and 9-hydroxyrisperidone, requiring dose modifications. 1
In pediatric patients, pharmacokinetics are similar to adults after correcting for body weight differences 1