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目的β1受体阻断剂联合血管紧张素Ⅱ受体拮抗剂在高血压治疗指南中,不做为优先推荐,但临床联合用药比较常见。选取美托洛尔(Metoprolo)为代表的选择性β1受体阻断剂,和厄贝沙坦(Irbesartan)为代表的非肽类血管紧张素Ⅱ受体AT1的拮抗药,研究它们在高血压患者体内的药代动力学-药效学结合模型,探讨二者降压作用特征,为临床个体化合理用药提供依据。方法将24例高血压患者分为2组,分别口服美托洛尔和厄贝沙坦,测定服药后不同时间的血药浓度和血压,计算药代动力学参数,采用Sheiner等提出的药动学药效学结合模型计算药效学参数,比较降压作用的实测值和预测值。结果高血压患者口服美托洛尔和厄贝沙坦体内代谢分别呈一室和二室模型,两药降压效应均滞后于血药浓度,存在逆时针滞后环,应用Sigmoid-Emax药效动力学模型研究效应室浓度与降压作用关系,美托洛尔和厄贝沙坦Ce(50)和Keo分别为(130.2±68.4)μg/L、(0.051±0.025)/min以及(380±140)μg/L、(0.54±0.08)/h,其降压作用的实测值和模型预测值接近。结论应用药动学、药效学结合模型研究美托洛尔和厄贝沙坦降压作用,可为其临床合理用药提供参考。
The purpose of β1 receptor blockers combined with angiotensin Ⅱ receptor antagonists in the guidelines for the treatment of hypertension, not as a priority recommendation, but clinical combination therapy is more common. We selected antagonists of selective β1 receptor blocker represented by Metoprolo and non-peptide angiotensin Ⅱ receptor AT1 represented by Irbesartan, Pharmacokinetics - pharmacodynamic binding model in patients to explore the characteristics of their antihypertensive effect, to provide the basis for clinical individual rational use of drugs. Methods Twenty-four patients with hypertension were divided into two groups. Metoprolol and irbesartan were orally administered. The plasma concentration and blood pressure were measured at different time points after administration. Pharmacokinetic parameters were calculated. Pharmacokinetics proposed by Sheiner et al. Pharmacodynamic model was used to calculate the pharmacodynamic parameters, comparing the measured and predicted values of antihypertensive effect. Results Metabolism of oral metoprolol and irbesartan in hypertensive patients showed one-compartment and two-compartment models, respectively. The antihypertensive effects of both drugs lagged behind the plasma concentrations, with anticlockwise hysteresis loops. Sigmoid-Emax pharmacodynamic The effects of metoprolol and irbesartan on Ce (50) and Keo were (130.2 ± 68.4) μg / L, (0.051 ± 0.025) / min and (380 ± 140 ) μg / L and (0.54 ± 0.08) / h, respectively. The measured values of the antihypertensive effect are close to those predicted by the model. Conclusions Application of pharmacokinetic and pharmacodynamic models to study the antihypertensive effect of metoprolol and irbesartan can provide a reference for its clinical rational use of drugs.