Schaefer K L, Porter J A
Kaiser Permanente, Wheat Ridge, CO 80033, USA.
Ann Pharmacother. 1996 Jun;30(6):625-36. doi: 10.1177/106002809603000611.
To describe a new class of antihypertensive agents, the angiotensin II receptor antagonists, with emphasis on the prototype losartan. Pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, and dosing guidelines.
A MEDLINE search of English-language literature published from 1966 through 1995 was performed. In addition, Merck and Co. provided bibliographic data on file for losartan.
Emphasis was placed on clinical and pharmacokinetic studies in humans. Controlled, double-blind studies were evaluated to assess the efficacy and adverse effect profile of losartan.
Losartan is a nonpeptide, competitive antagonist of the type I angiotensin II receptor. In comparative clinical trials, losartan appears to have antihypertensive efficacy similar to that of the angiotensin-converting enzyme (ACE) inhibitors. Losartan is well tolerated, with an adverse effect profile similar to that of placebo and a reduced incidence of cough versus that with ACE inhibitors. A combination product consisting of losartan 50 mg and hydrochlorothiazide 12.5 mg has also received approval for the treatment of hypertension. The combination product is not indicated for initial therapy, but is recommended for patients who do not respond adequately to losartan monotherapy. The angiotensin II receptor antagonists are also being investigated for beneficial effects in patients with ventricular hypertrophy, renal disease, and heart failure.
Losartan, the first angiotensin II receptor antagonist to receive approval for use in the US, appears to be an effective new antihypertensive agent with an adverse effect profile similar to that of placebo. Losartan may be an alternative for patients who cannot tolerate ACE inhibitors. However, the effect of losartan on mortality remains to be evaluated. The role of the angiotensin II receptor antagonists in areas such as ventricular hypertrophy, renal function, and heart failure has yet to be determined.
描述一类新型抗高血压药物——血管紧张素II受体拮抗剂，重点介绍其原型药物氯沙坦。回顾其药代动力学数据、临床试验、不良反应、药物相互作用及给药指南。
对1966年至1995年发表的英文文献进行了MEDLINE检索。此外，默克公司提供了氯沙坦的存档文献数据。
重点关注人体的临床和药代动力学研究。对对照双盲研究进行评估，以评估氯沙坦的疗效和不良反应情况。
氯沙坦是一种非肽类、I型血管紧张素II受体竞争性拮抗剂。在比较临床试验中，氯沙坦的降压疗效似乎与血管紧张素转换酶（ACE）抑制剂相似。氯沙坦耐受性良好，不良反应情况与安慰剂相似，咳嗽发生率低于ACE抑制剂。一种由50毫克氯沙坦和12.5毫克氢氯噻嗪组成的复方制剂也已获批用于治疗高血压。该复方制剂不用于初始治疗，但推荐给氯沙坦单药治疗效果不佳的患者。血管紧张素II受体拮抗剂也正在研究对心室肥厚、肾病和心力衰竭患者的有益作用。
氯沙坦是美国首个获批使用的血管紧张素II受体拮抗剂，似乎是一种有效的新型抗高血压药物，不良反应情况与安慰剂相似。对于不能耐受ACE抑制剂的患者，氯沙坦可能是一种替代药物。然而，氯沙坦对死亡率的影响仍有待评估。血管紧张素II受体拮抗剂在心室肥厚、肾功能和心力衰竭等领域的作用尚未确定。
