Abstract: OBJECTIVE To establish a population pharmacokinetic-pharmadynamic(PK-PD) model of clopidogrel in patients with coronary heart disease, so as to provide clinical basis for early diagnosis and intervention of clopidogrel resistance.METHODS The 101 patients with coronary heart disease were prospectively collected. Clopidogrel active metabolite (Clop-AM) concentration and maximum platelet aggregation rate(MAR) were used as pharmacokinetic and pharmacodynamic indicators. Nonlinear mixed effect model was used to quantitatively investigate the factors affecting clopidogrel resistance, such as gender, age, body mass index(BMI), CYP2C19 genotype and complications, and to establish a population PK-PD models of clopidogrel in patients with coronary heart disease.RESULTS The typical population value of the apparent clearance rate of Clop-AM was 2 910 L·h^-1. BMI had an effect on the apparent clearance of Clop-AM. The final model formula was CL=2 910×(BMI/25.09)×3.22. The mean prediction error(MPE) and the root mean square prediction error(RMSE) were PK/PD: MPE=0.14, RMSE=10.77; PK: MPE=0.26, RMSE=2.91, PD: MPE=-0.05, RMSE=17.10.CONCLUSION The population PK-PD model of clopidogrel in patients with coronary heart disease has been preliminarily established. Clop-AM clearance is accelerated in patients with high BMI. It has certain reference value for individualized administration of clopidogrel.