External validation of a therapeutic window for risperidone in children with autism spectrum disorder.

Although risperidone is an effective pharmacological intervention for managing disruptive behaviour in children with autism spectrum disorder, it may induce metabolic side effects. This study aimed to externally validate the population pharmacokinetic (popPK) model and the therapeutic window of 3.5-7 ng/mL of risperidone and 9-OH-risperidone, developed with data of the SPACe Study. For this external validation, data from the German Therapeutic Drug Monitoring (TDM) Service and TDM-VIGIL Study was used in nonlinear mixed-effects modelling to evaluate popPK model performance and in receiver operating curve analyses to define the therapeutic window. Population predictions of the popPK model showed underprediction for risperidone concentrations, but individual predictions were fairly accurate. Receiver operating curve analyses resulted in a therapeutic window of 5.0-8.0 ng/mL. The popPK model seems suitable for use in TDM. Because the current analysis included only a few low sum trough concentrations, we suggest maintaining the therapeutic window of 3.5-7.0 ng/mL.