Comparison of Iterative-Two Stage and Bootstrap Sampling Approaches in the Development of a Population Pharmacokinetic Model

The kinetics of an antineoplastic drug, suramin, described by a three-compartment, open, linear model is studied in this report. A population pharmacokinetic model, describing the pharmacokinetics of suramin, was developed using the iterative-two stage approach, with maximum a posteriori-Bayesian priors. It was further validated using data from a subsequent study (validation data set). The population pharmacokinetic parameters were also estimated by generating bootstrap samples from the validation data set. When the prior distribution was close to the population distribution, there was no significant difference between the estimates obtained using the iterative-two stage approach and the bootstrap approach. However, when estimating population pharmacokinetic parameters, the iterative-two stage approach was less sensitive to prior distribution specification