Model-based Meta-analysis of population pharmacokinetic models for paclitaxel in humans, rats and mice / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a quantitative method to evaluate the relationship on the PK parameters of paclitaxel among different species by using the model-based Meta-analysis, and provide a reference for species extrapolation and dose determination of new drug research and development. METHODS: Relevant literatures were searched in Pub-Med, CNKI, WanFang and other databases, and all search results were filtrated with the criteria and classified according to species. Using NONMEM to construct the model for human, rats and mice, respectively. Evaluating the performance of the model with normalized prediction distribution errors (NPDE), and calculating the correlation coefficient of species with allometric scaling method. RESULTS: The nonlinear mixed-effects model (NONMEM) was developed to describe the paclitaxel PK profiles for mice, rats and humans. A two-compartment pharmacokinetic model fitted the data well, and consistent with the reported results. The models were evaluated by NDPE, the final model was accurate and reliable. The allometric scaling of CL and Vtotal among three different species for paclitaxel was r2=0.9974 and r2=0.9372, respectively. CONCLUSION: Take paclitaxel for example, established the model-based meta-analysis, successfully, and evaluated the correlation on the PK parameters of paclitaxel among different species quantitatively.