Half-Life of Risperidone
In patients with normal liver and kidney function, risperidone has a half-life of approximately 3 hours in extensive metabolizers and 20 hours in poor metabolizers, while its active metabolite 9-hydroxyrisperidone has a half-life of approximately 21 hours in extensive metabolizers and 30 hours in poor metabolizers. 1
Understanding the Active Moiety
The clinical effect of risperidone results from the combined concentrations of risperidone plus 9-hydroxyrisperidone, as the metabolite has similar pharmacological activity to the parent drug. 1 This combined "active fraction" has an overall mean elimination half-life of approximately 20 hours, regardless of metabolizer status. 1, 2
Metabolizer Status Impact
The key determinant of risperidone's half-life is CYP 2D6 metabolizer status:
Extensive metabolizers: Convert risperidone rapidly to 9-hydroxyrisperidone, resulting in a risperidone half-life of ~3 hours and 9-hydroxyrisperidone half-life of ~21 hours 1, 2
Poor metabolizers: Convert risperidone much more slowly, resulting in a risperidone half-life of ~19-20 hours and 9-hydroxyrisperidone half-life of ~30 hours 1, 2
Approximately 6-8% of Caucasians and a very low percentage of Asians are poor metabolizers 1
Clinical Implications
Despite the differences in individual component half-lives, the active moiety (risperidone + 9-hydroxyrisperidone) maintains a consistent half-life of approximately 20-23 hours across both metabolizer phenotypes. 1, 2, 3 This allows for:
- Steady state to be reached within 1 day for risperidone and within 5 days for the active fraction 2
- Potential for twice-daily or even once-daily dosing based on the 23-hour half-life of the active moiety 3
Important Caveats
Research in Chinese female schizophrenic patients demonstrated a shorter risperidone half-life of 3.2 hours but a longer 9-hydroxyrisperidone half-life of 24.7 hours, with large interindividual variations. 4 This highlights that while the FDA label provides standard values, individual pharmacokinetic parameters can vary considerably, particularly across different ethnic populations. 4