Population Pharmacokinetics and Dosing Simulations for Paliperidone Palmitate 351 mg as Alternative Maintenance Doses in Patients With Schizophrenia or Schizoaffective Disorder.

Objective: Once-monthly paliperidone palmitate (PP1M) extended-release injectable suspension is approved for the treatment of adults with schizophrenia or schizoaffective disorder. A 351 mg dose of PP1M (LY03010 [brand name Erzofri]) became available in the US in April 2025 and is approved as a single initiation injection followed by recommended monthly maintenance doses up to 234 mg. The objective of this study was to investigate steady-state paliperidone exposure following administration of 351 mg as a maintenance dose at different dosing intervals using population pharmacokinetic (popPK) analysis. Methods: A popPK model was developed using Nonlinear Mixed Effects Modeling (NONMEM) based on the paliperidone concentration data from 2 phase 1 studies for LY03010. Plasma paliperidone exposures based on model simulations were summarized. Results: Simulated plasma concentration-time profiles demonstrated that LY03010 351 mg every 4 weeks (Q4W) produced steady-state paliperidone exposure comparable to 234 mg every 3 weeks (Q3W) based on analysis of Cmax,ss and Ctrough,ss. Simulated data indicated that administration of LY03010 351 mg every 6 weeks (Q6W) provided similar paliperidone exposure to 234 mg PP1M Q4W at steady state. Simulation of LY03010 351 mg every 8 weeks (Q8W) showed that Cmax,ss of paliperidone fell in-between that of 234 mg Q4W and 156 mg Q4W while Ctrough,ss was comparable to that of 117 mg Q4W. Conclusions: PopPK simulations suggest that LY03010 351 mg may provide alternative treatment options as a maintenance dose at different dosing intervals. Currently, there are no clinical data to support the alternative dosing regimens. Trial Registration: ClinicalTrials.gov identifiers: NCT04572685 and NCT04922593.