Prediction of the bioequivalence of different crystal forms of rifampicin based on physiologically based pharmacokinetic model / 中国药科大学学报

@#The physiologically based pharmacokinetic (PBPK) modeling strategy was adopted to predict the pharmacokinetic behavior of crystal forms I and II of rifampicin in humans, which was used to determine whether the two were bioequivalent.After conducting studies in vitro of the two crystal forms, a rat PBPK model was established based on the pharmacokinetic data of intravenous administration in rats.The model was optimized by the pharmacokinetic data of oral administration in rats.Species were extrapolated to healthy humans, and the extrapolation model was used to predict such pharmacokinetic behaviors as the drug-time curve, absorption site, and absorption amount of the two crystal forms of rifampicin in healthy humans.The prediction results of the healthy human model showed that the cmax of form I and form II rifampicin were 8.42 and 10.35 μg/mL, tmax were 0.40 and 0.32 h,and AUC0-t were both 62.90 μg·h/mL.According to the prediction results of absorption, neither crystal form I nor crystal form II rifampicin was absorbed in the stomach, yet both were completely absorbed in the intestinal tract, with both the absorption site and the absorption amount were basically the same.The pharmacokinetic parameters of both crystal forms I and II of rifampicin were very close, which could indicate bioequivalence.

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

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.