Abstract: Objective In hypertension treatment guidelines,Beta-1 receptor antagonist combined with angiotensin Ⅱ receptor antagonist are not be recommended for priority.But it is common for the combination of both medicines in clinical practice.In order to provide evidence for the rational use of clinical drug,metoprolol were selected as selective beta 1 receptor blocker,Irbesartan was chosen as the representative of the angiotensin receptor Ⅱ.In patients with high blood pressure,a pharmacokinetic pharmacodynamics-combination model was established,to discuss the antihypertensive effect characteristics of the two drugs. Methods A total number of 24 patients with hypertension were divided into two groups,one group was given metoprolol,another group were given Irbesartan.The blood drug concentration and blood pressure were measured.To calculate the pharmacokinetic parameters,the blood drug concentration and blood pressure were measured at different time.The pharmacodynamics parameters were also determined using combined pharmacokinetic-pharmacodynamics(PK-PD) model presented by Sheiner et al.The data of reduced blood pressure were determined and compared with the predicted data. Results The pharmacokinetic profiles of metoprolol and irbesartan were fitted to one and two compartment model respectively.There was an anticlockwise hysteresis loop between antihypertensive effect and plasma concentrations of the agents.The relationship between antihypertensive effect and concentration of effect compartment of the agents was investigated using Sigmoid-Emax model.The data of Ce(50) and Keo for metoprolol and irbesartan were (130.2±68.4)μg/L,(0.051±0.025)/min and (380±140)μg/L,(0.54±0.08)/h,respectively.The determined data of the antihypertensive effect was close to those predicted. Conclusion To Study the antihypertensive effect of metoprolol and irbesartan with PK-PD model may be more rational for the clinical medication.