Population pharmacokinetics of rotigotine extended‐release microspheres for intramuscular injection in patients with early‐stage Parkinson's disease

Aims Rotigotine extended‐release microspheres is a weekly intramuscular injection formulation to treat Parkinson's disease. This study aimed to develop a population pharmacokinetics (PK) model for rotigotine extended‐release microspheres to investigate its PK ethnic differences. Methods Data for the study were obtained from three studies in China, Japan and the US. The population PK model was developed using the Phoenix NLME 8.3.5 software. Two parallel absorption models were created to include both zero‐ and first‐order absorptions. The elimination phase was evaluated for one‐ and two‐compartment linear models. Moreover, covariates including sex, body weight, body mass index, albumin, creatinine clearance and race were input into the model using a stepwise covariate method. Results We constructed a one‐compartment linear model with the first parallel absorption model identified as the best‐fitting model. Simulation results in patients with lighter body weight (45 kg) exhibited a 27% increase in C max,ss and a 31% increase in AUC tau,ss compared to those with median body weight (65 kg). Patients with heavier body weight (103 kg) showed a 27% decrease in C max,ss and a 29% decrease in AUC tau,ss compared to the median body weight group. Asian patients displayed only a 21% increase in C max,ss and a 6% increase in AUC tau,ss compared to non‐Asian. While we could not fully conclude that race does not affect rotigotine exposure, dosage adjustments based on race were not deemed necessary. Conclusions Exposure differences were mainly attributed to body weight, while dose adjustments were not needed for patients of different racial identities.