Objectives To characterize the population pharmacokinetics (PPK) of lurasidone in Chinese psychiatric inpatients and to quantify the sources of inter-individual variability, with a specific focus on the impact of valproate (VPA) co-medication and age on drug exposure. Methods Routine therapeutic drug monitoring (TDM) data were collected from 156 patients (providing 212 serum concentrations). A PPK model was developed utilizing a nonlinear mixed-effects modeling approach (NONMEM). Model performance was assessed via goodness-of-fit plots, normalized prediction distribution errors (NPDE), and bootstrap analysis. Additionally, model-based simulations were performed to estimate concentration profiles stratified by age and VPA co-medication. Results A one-compartment model with first-order absorption and elimination best described the data. The typical estimate for apparent clearance (CL/F) was 339 L·h -1 . Age and concomitant VPA were identified as significant covariates. VPA co-administration increased CL/F by 47.7%, leading to significantly reduced systemic exposure. Notably, the majority of observed steady-state concentrations (3–11 ng/mL) fell below the lower limit of the AGNP reference range. Conclusion The pharmacokinetics of lurasidone in Chinese inpatients were effectively characterized by the established PPK model. Lurasidone exposure in this population is generally lower than the AGNP reference range, particularly in patients receiving VPA. Age and VPA co-medication are critical determinants of CL/F. These findings suggest that TDM interpretation should be adjusted for these factors, and optimal concentration targets for Chinese patients may need to be revisited.
Yang et al. (Tue,) studied this question.
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