AN APPLICATION OF BAYESIAN POPULATION PHARMACOKINETIC-PHARMACODYNAMICMODELS TO DOSE RECOMMENDATION

Population pharmacokinetic data consists of dose histories, individual covariates and measured drug concentrations with associated sampling times. Population pharmacodynamic data consist of dose histories, cova riates and some response measure. Population analyses, whether they be pharmacokinetic or pharmacodynamic attempt to explain the variability observed in the recorded measurements and are increasingly being seen as an important aid in drug development. In this paper a general Baye sian population pharmacokinetic/pharmacodynamic model is described and an analysis of data for the drug recombinant hirudin is presented. Th e model we use allows for both outliers and censoring in the concentra tion data and outlying individual pharmacokinetic parameters. We attem pt to address directly important questions such as recommended dose si ze using predictive distributions for response.