TY - JOUR AU - Yang Juan AU - Li Lu-jin AU - Wang Kun AU - He Ying-chun AU - Sheng Yu-cheng AU - Xu Ling AU - Huang Xiao-hui AU - Guo Feng AU - Zheng Qing-shan PY - 2016 TI - Race differences: modeling the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients JF - Acta Pharmacologica Sinica; Vol 32, No 1 (January 2011): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - Aim: To evaluate race differences in the pharmacodynamics of rosuvastatin in Western and Asian hypercholesterolemia patients using a population pharmacodynamic (PPD) model generated and validated using published clinical efficacy trials. Methods: Published studies randomized trials with rosuvastatin treatment for at least 4 weeks in hypercholesterolemia patients were used for model building and validation. Population pharmacodynamic analyses were performed to describe the dose-response relationship with the mean values of LDL-C reduction (%) from dose-ranging trials using NONMEM software. Baseline LDL-C and race were analyzed as the potential covariates. Model robustness was evaluated using the bootstrap method and the data-splitting method, and Monte Carlo simulation was performed to assess the predictive performance of the PPD model with the mean effects from the one-dose trials. Results: Of the 36 eligible trials, 14 dose-ranging trials were used in model development and 22 one-dose trials were used for model prediction. The dose-response of rosuvastatin was successfully described by a simple Emax model with a fixed E 0 , which provided a common E max and an approximate twofold difference in ED 50 for Westerners and Asians. The PPD model was demonstrated to be stable and predictive. Conclusion: The race differences in the pharmacodynamics of rosuvastatin are consistent with those observed in the pharmacokinetics of the drug, confirming that there is no significant difference in the exposure-response relationship for LDL-C reduction between Westerners and Asians. The study suggests that for a new compound with a mechanism of action similar to that of rosuvastatin, its efficacy in Western populations plus its pharmacokinetics in bridging studies in Asian populations may be used to support a registration of the new compound in Asian countries. UR - http://www.chinaphar.com/article/view/4904