Population Pharmacokinetics of Naoqingzhiming Tablets a Novel Drug for Vascular Dementia in Healthy Chinese Subjects

Author(s): Xin Liu, Pingping Lin, Ting Li, Ping Shi, Chenjing Wang, Lujin Li, Yu Cao

Objective The aims of this study was to develop a population pharmacokinetic model to characterize the pharmacokinetics of Naoqingzhiming tablets (ingredient: echinacoside) following single and multiple doses in healthy Chinese subjects, and to identify covariates that might explain variability in exposure following oral administration. Methods Model development was achieved using data from a single- and multiple-dose studies. 1497 blood concentrations were available for population pharmacokinetics model. Population pharmacokinetic modelling was conducted using nonlinear mixed-effects modelling (NONMEM) software to estimate population pharmacokinetic parameters. Results A two-compartment model with first order absorption and elimination was found to best describe the pharmacokinetics of Naoqingzhiming tablets. The final model included aspartate aminotransferase (AST) as a covariate on apparent volume of distribution (V/F). The final pharmacokinetic parameter estimates were apparent clearance, 2510L/h; apparent volume of distribution, 11200L; and lag time, 0.141h. Conclusion The population pharmacokinetic model for Naoqingzhiming tablets identified the relationship between pharmacokinetic parameters and covariates, apparent volume of distribution was related to aspartate aminotransferase.

Echinacoside, Population Pharmacokinetics, Modeling, Naoqingzhiming Tablets

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