Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, 305-764, Korea.
Arch Pharm Res. 2010 Sep;33(9):1411-8. doi: 10.1007/s12272-010-0915-9. Epub 2010 Oct 14.
To examine drug synergism between angiotensin II AT1-receptor blocker and Ca(2+) channel blocker for lowering blood pressure (BP), telmisartan and lercanidipine were orally injected into to telemetered-spontaneous hypertensive rats and BP was monitored. The highest doses of both drugs (7.66 mg/kg of telmisartan and 1.92 mg/kg of lercanidipine) were clinically relevant at 80 and 20 mg human equivalent doses, respectively, and denoted as dose 1. After constructing the dose-response curve using 0 (vehicle-treated control), 1/16, 1/8, 1/4, 1/2 and 1 doses, all possible combinations of both drugs were tested. Drug synergism in combination therapy of telmisartan with lercanidipine was assessed by calculating the interaction index (γ) as evaluated by γ < 1. We found statistically significant drug synergism in the investigated (telmisartan: lercandipine) combinations of (1/8:1/4), (1/4:1) and (1/8:1). Our results suggest that the combination therapy of telmisartan and lercanidipine at lower doses are effective in lowering BP, and also reduce side effects caused by maximal doses of each drug. Therefore, drug combination of AT1-receptor blocker with Ca(2+) channel blocker is a clinically important tool for the management of hypertension and hypertension-related cardiovascular risks.
为了研究血管紧张素 II AT1 受体阻滞剂和钙通道阻滞剂在降低血压（BP）方面的协同作用，替米沙坦和乐卡地平被口服注射到遥测自发性高血压大鼠中，并监测 BP。两种药物的最高剂量（替米沙坦 7.66mg/kg 和乐卡地平 1.92mg/kg）分别在 80 和 20mg 人等效剂量下具有临床相关性，分别表示为剂量 1。在使用 0（载体处理对照）、1/16、1/8、1/4、1/2 和 1 剂量构建剂量反应曲线后，测试了两种药物的所有可能组合。通过计算评价为γ<1 的相互作用指数（γ）来评估替米沙坦与乐卡地平联合治疗中的药物协同作用。我们发现在所研究的替米沙坦与乐卡地平的组合治疗中（1/8:1/4）、（1/4:1）和（1/8:1）中存在统计学显著的药物协同作用。我们的结果表明，替米沙坦和乐卡地平的联合治疗在较低剂量下有效降低 BP，并且还降低了每种药物最大剂量引起的副作用。因此，AT1 受体阻滞剂与钙通道阻滞剂的药物联合是管理高血压和高血压相关心血管风险的重要临床工具。
