Population Pharmacokinetics of Risperidone and Paliperidone in Schizophrenia: A Systematic Review

Background: The primary treatment of schizophrenia is pharmacotherapy with antipsychotic agents, such as risperidone and paliperidone. Population pharmacokinetic (PopPK) modelling plays a crucial role in optimising therapy by predicting of plasma concentrations, therapeutic efficacy, and the risk of adverse effects using model informed precision dosing. Objectives: This systematic review examined the PopPK models of risperidone and paliperidone in patients diagnosed with schizophrenia based on the available scientific evidence. Methods: A systematic review of the health science databases was conducted. The inclusion criteria were original articles published in peer-reviewed journals, studies focusing on the development of original PopPK models of risperidone and paliperidone, and clinical studies. The exclusion criteria were full-text articles that could not be retrieved; studies not including subjects diagnosed with schizophrenia or schizoaffective disorders; and studies that did not investigate risperidone or paliperidone. Results: A total of 19 studies developing PopPK models were analysed, including one- or two-compartment PopPK model structures. Interindividual variability in the pharmacokinetic parameters was shown to be influenced by factors such as CYP2D6 activity, renal function, body mass index, and sex. Parameter estimation revealed high variability in clearance and volume of distribution. Conclusion: Numerous PopPK models for risperidone and paliperidone have been published with a detailed characterisation of absorption, metabolism, and elimination. Therefore, future research should focus on the external validation of these models to facilitate their integration into clinical practice and optimise individualised dosing, ultimately improving treatment efficacy and safety across diverse patient populations.