Brunner H R
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Am J Hypertens. 1997 Dec;10(12 Pt 2):311S-317S. doi: 10.1016/s0895-7061(97)00391-9.
This article reviews the pharmacokinetics and pharmacodynamics of angiotensin II (AII) receptor antagonists (AIIRA), with particular focus on the novel compound irbesartan. Irbesartan has the highest oral bioavailability in its class (60% to 80%) and, unlike valsartan, its absorption is not affected by food. Irbesartan displays linear, dose related pharmacokinetics and, with the exception of tasosartan's active metabolite, has the longest elimination half-life of the AIIRA (11 to 15 h). Irbesartan exhibits the lowest amount of protein binding, limiting its potential for drug interactions. No drug interactions with irbesartan have been identified. Unlike losartan, candesartan, and tasosartan, irbesartan does not require biotransformation for AII blockade. The pharmacokinetics of irbesartan are not altered in renally or hepatically impaired patients, probably owing to excretion characteristic by both biliary and renal routes, or by differences in gender or age. Within its therapeutic dose range (150 to 300 mg), irbesartan shows sustained, dose related blockade 24 h after dosing. Irbesartan lowers blood pressure in a dose related manner up to 300 mg daily. Some clear differences in pharmacokinetics and pharmacodynamics exist among the AIIRA, which may have clinical implications.
本文综述了血管紧张素II（AII）受体拮抗剂（AIIRA）的药代动力学和药效学，尤其聚焦于新型化合物厄贝沙坦。厄贝沙坦在同类药物中具有最高的口服生物利用度（60%至80%），且与缬沙坦不同，其吸收不受食物影响。厄贝沙坦呈现线性、剂量相关的药代动力学，并且除替米沙坦的活性代谢产物外，其消除半衰期是AIIRA中最长的（11至15小时）。厄贝沙坦的蛋白结合量最低，限制了其发生药物相互作用的可能性。尚未发现与厄贝沙坦存在药物相互作用。与氯沙坦、坎地沙坦和替米沙坦不同，厄贝沙坦不需要生物转化即可进行AII阻断。厄贝沙坦的药代动力学在肾或肝功能受损患者中未发生改变，这可能归因于其通过胆汁和肾脏途径排泄的特性，或性别或年龄差异。在其治疗剂量范围内（150至300毫克），厄贝沙坦在给药后24小时显示出持续的、剂量相关的阻断作用。厄贝沙坦以剂量相关的方式降低血压，每日剂量高达300毫克。AIIRA之间在药代动力学和药效学方面存在一些明显差异，这可能具有临床意义。
