Half-Life of Risperidone's Active Metabolite
The half-life of paliperidone (9-hydroxy-risperidone), which is the active metabolite of risperidone, is approximately 23 hours. 1
Pharmacokinetic Profile of Paliperidone
Paliperidone is the major active metabolite of risperidone and has distinct pharmacokinetic properties:
- Terminal elimination half-life: approximately 23 hours 1, 2
- Steady-state concentrations are achieved within 4-5 days of dosing 1
- Peak plasma concentrations are reached approximately 24 hours after dosing 1, 2
- The pharmacokinetics are dose-proportional within the available dose range 1
- Mean steady-state peak-to-trough ratio for a 9 mg dose is 1.7 (range 1.2-3.1) 1
Metabolism and Elimination
The metabolism and elimination of paliperidone differs significantly from its parent compound:
- Renal excretion is the major route of elimination for paliperidone 2
- Although in vitro studies suggested roles for CYP2D6 and CYP3A4 in paliperidone metabolism, in vivo results indicate these enzymes play a limited role in overall elimination 1
- Following administration, the (+) and (-) enantiomers of paliperidone interconvert, reaching an AUC (+) to (-) ratio of approximately 1.6 at steady state 1
Clinical Implications
The 23-hour half-life of paliperidone has several important clinical implications:
- Once-daily dosing is sufficient for maintaining therapeutic levels 2
- No initial dose titration is required when starting paliperidone extended-release 2
- Paliperidone may be preferred over risperidone when liver disease, drug-drug interactions, or other alterations in metabolism make appropriate risperidone dosing difficult to determine 2
- The extended half-life provides more stable plasma drug concentrations over a 24-hour period compared to medications with shorter half-lives 3
Comparison to Other Antipsychotics
In a prospective cohort study comparing short-acting versus long half-life antipsychotics, medications with longer half-lives like risperidone (and by extension its metabolite paliperidone) showed continued improvement in delirium symptoms at day 7 of treatment 4.
Understanding the 23-hour half-life of paliperidone is essential for proper dosing, monitoring, and clinical decision-making when using risperidone in psychiatric practice.