Switching Patients With Schizophrenia From Intramuscular Paliperidone Palmitate Once Monthly to TV-46000, a Long-Acting Subcutaneous Antipsychotic: An Exploration of Population Pharmacokinetic–Based Strategies
Background: This analysis used population pharmacokinetic (PopPK) modeling to characterize dosing conversions and switching strategies from intramuscular paliperidone palmitate once monthly (PP1m) to TV-46000, a long-acting subcutaneous antipsychotic formulation of risperidone, once monthly (q1m) or once every 2 months (q2m).
Methods: Total active moiety (risperidone + paliperidone) concentration–time profiles were simulated based on published PopPK models for PP1m and TV-46000 with virtual populations of 5000 patients. Percentage ranges (median Cmin divided by oral risperidone median Cmin minus 1, median Cmax divided by oral risperidone median Cmax) were evaluated.
Results: Simulations revealed the most comparable doses of TV-46000 to PP1m were 50mg-q1m/100mg-q2m TV-46000 to 78mg-PP1m (2mg/day oral comparable), 75mg-q1m/150mg-q2m TV-46000 to 117mg-PP1m (3 mg/day oral comparable), 100mg-q1m/200mg-q2m TV-46000 to 156mg-PP1m (4mg/day oral comparable), and 125mg-q1m/250mg-q2m TV-46000 to 234mg-PP1m (5 or 6mg/day oral comparable). Within each oral-comparable reference range (median Cmin to Cmax), TV-46000 ranges trended higher relative to PP1m, with a higher range estimated for TV-46000 q2m than q1m. Two potential switching scenarios were identified, both starting 4 weeks after the last PP1m injection: 1) a comparable-dose switch, or if clinicians seek to reduce the initial post-switch Cmax peak, 2) transition to a lower q1m dose for 6 months (6 injections) or lower q2m dose for 2 months (1 injection) followed by 1:1 comparable dosing.
Conclusion: Switching to TV-46000 4 weeks after the last PP1m injection yielded generally comparable pharmacokinetic parameters upon steady-state. Clinician discretion will determine which switching strategy is appropriate for their context.
