Author/Authors :
Huang, Xiao-hui Anhui Medical University - College of Pharmacy, Center of Pharmacokinetics, China , Wang, Kun Shanghai University of Chinese Medicine - Center for Drug Clinical Research, China , Huang, Ji-han Shanghai University of Chinese Medicine - Center for Drug Clinical Research, China , Xu, Ling Shanghai University of Chinese Medicine - Center for Drug Clinical Research, China , Li, Lu-jin Shanghai University of Chinese Medicine - Center for Drug Clinical Research, China , Sheng, Yu-cheng Shanghai University of Chinese Medicine - Center for Drug Clinical Research, China , Zheng, Qing-shan Shanghai University of Chinese Medicine - Center for Drug Clinical Research, China
Abstract :
The purpose of this study was to use the stochastic simulation and estimation method toevaluate the effects of sample size and the number of samples per individual on the model development and evaluation. The pharmacokinetic parameters and inter- and intra-individual variation were obtained from a population pharmacokinetic model of clinical trials of amlodipine. Stochastic simulation and estimation were performed to evaluate the efficiencies of different sparse sampling scenarios to estimate the compartment model. Simulated data were generated a thousand times and three candidate models were used to fit the 1000 data sets. Fifty-five kinds of sparse sampling scenarios were investigated and compared. The results showed that, 60 samples with three points and 20 samples with five points are recommended, and the quantitative methodology of stochastic simulation and estimation is valuable for efficiently estimating the compartment model and can be used for other similar model development and evaluation approaches.
Keywords :
Amlodipine , Sparse sampling , Model estimation , Population pharmacokinetics
