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.