DEVELOPMENT OF PHYSIOLOGICALLY BASED PHARMACOKINETIC MODEL FOR THE IMMEDIATE RELEASE ROPINIROLE TABLETS

Ropinirole is a dopamine receptor agonist with high inter-individual variability in pharmacokinetic parameters. Physiologically based pharmacokinetic (PBPK) modeling allows predicting drug pharmacokinetic behavior while accounting for individual demographic and physiological parameters. Considering that ropinirole is used in patients of different ages and disease states, a PBPK model could be of potential use in informing clinical trials or new formulation development. The aim of this study was to develop a PBPK model for ropinirole and investigate whether the developed model will be able to predict pharmacokinetics in patient populations. Within this paper, a PBPK model for the immediate release ropinirole tablets was developed and verified against observed data from 11 clinical trials. The model reasonably predicted pharmacokinetics of ropinirole in healthy volunteers and patient populations. Predicted ropinirole PK parameters were within 2-fold of the observed values. The model is able to predict ropinirole pharmacokinetics in healthy volunteers, Parkinson's disease patients, and restless legs syndrome patients.