A computationally efficient approach for the design of population pharmacokinetic studies.
A computationally efficient procedure was devised for designing experiments in which population pharmacokinetic parameters are estimated. The method, referred to as the large-sample approach, evaluates the variances of parameter estimates for a population pharmacostatistical model. The procedure utilizes the NONMEM program and requires a single simulation that assumes many, say 1000, subjects. The approach reduced CPU time by about a factor of 50 when compared with the evaluation of the same variances by the direct simulation of experiments. The large-sample and simulation approaches yielded generally similar values for the variances of parameter estimates. The variances calculated by the large-sample approach were, in the case of a simple model, close to the expected variances. The proposed method identified correctly the imprecise parameter estimates but somewhat underestimated their variances.
Wang
J
J
Department of Pharmacology, University of Toronto, Ontario, Canada.
Endrenyi
L
L
D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D010599:Pharmacokinetics; D012107:Research Design; D012494:Sampling Studies