瑞格列奈是治疗2 型糖尿病的一线药物，血管紧张素Ⅱ型受体拮抗剂（ARB）是糖尿病合并高血压患者的首选降压药。瑞格列奈是肝转运体OATP1B1 的底物，而ARB是OATP1B1 的抑制剂和/或底物。迄今未见ARB对瑞格列奈药动/药效(PK/PD)的研究报道。我们前期研究发现：① 体外厄贝沙坦抑制OATP1B1活性最强。② 合用厄贝沙坦可使瑞格列奈的峰浓度增加约70%，半数受试者出现低血糖反应，而低血糖会导致不同程度的脑细胞损害甚至危及生命。本项目拟在前期工作基础上，定量研究这一相互作用。包括(1) 在OATP1B1 稳转细胞系阐明厄贝沙坦对瑞格列奈药动影响的机制；(2) 构建基于OATP1B1 的生理药动学的相互作用模型。(3)模拟不同人群、不同给药方案下厄贝沙坦对瑞格列奈的定量影响，按模拟结果开展临床试验，以患者的PK/PD 数据对模型进行验证和优化。该研究为瑞格列奈个体化用药提供参考。

Repaglinide is a first-line drug for the treatment of type 2 diabetes, Angiotensin II receptor antagonists (ARBs) are the preferred antihypertensive drugs for diabetic patients with hypertension. Repaglinide is a substrate of the liver uptake transporter OATP1B1, while ARBs are inhibitors and/or substrates of OATP1B1. To our knowledge,there is no report about drug-drug interaction between ARBs and repaglinide.Our previous studies showed: ①irbesartan exhibited strongest inhibition activity on OATP1B1 in vitro. ② irbesartan could increase repaglinide peak concentration by approximate 70%, half of the subjects experienced hypoglycaemic reaction. Hypoglycaemia can cause varying degrees of brain cell damage and even life-threatening. This research is designed to quantitatively study this interaction: (1)clarify the effects of irbesartan on repaglinide pharmacokinetics in OATP1B1 stable transfected cell lines; (2)establish drug interaction model based on OATP1B1 physiological pharmacokinetics;(3) simulate the quantitative effects of irbesartan on repaglinide pharmacokinetics/ pharmacodynamics (PK/PD) in different populations and under different dosing regimens; and select the most appropriate protocol according to simulation results to conduct clinical trials, use actual PK / PD data to validate and optimize the model. This study will provide reference for individualized medicine of repaglinide.