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

This research checked how well doctors can predict the right amount of risperidone medication for autistic children. Risperidone helps manage challenging behaviors but can cause side effects. The study confirmed that blood level measurements between 3.5-7.0 ng/mL work well for treatment monitoring, helping doctors give the right dose while avoiding harmful effects.

This study externally validated a population pharmacokinetic model for risperidone, an antipsychotic medication used to manage disruptive behaviors in children with autism spectrum disorder. Researchers used German therapeutic drug monitoring data to test a previously established therapeutic window of 3.5-7 ng/mL for combined risperidone and 9-OH-risperidone concentrations. The validation showed the model was suitable for therapeutic drug monitoring, though it slightly underpredicted risperidone concentrations at population level. New analysis suggested a therapeutic window of 5.0-8.0 ng/mL, but researchers recommend maintaining the original 3.5-7.0 ng/mL range due to limited low concentration data in their validation sample.

Supports use of therapeutic drug monitoring for risperidone in autistic children. Validates 3.5-7.0 ng/mL therapeutic window for clinical decision-making. Model can guide personalized dosing to optimize treatment outcomes while minimizing metabolic side effects.

Sample size not reported. Limited representation of low concentration measurements in validation dataset. External validation used different population characteristics from original model development study.

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.