Meredith P
Department of Medicine and Therapeutics, University of Glasgow, UK.
Blood Press Suppl. 2000;1:23-6.
Epidemiological evidence suggests that optimal blood pressure control requires strategies that lower blood pressure consistently and fully throughout 24 h. In order to maximize compliance, antihypertensive agents also need to be well tolerated and effective when administered at a convenient once-daily dose. The new angiotensin II type 1 (AT1) receptor blocker candesartan binds tightly to, and dissociates slowly from, the AT1-receptor and thereby provides long-lasting suppression of the renin-angiotensin system. This is likely to explain its pronounced antihypertensive efficacy, which is maintained smoothly over 24 h. The trough-to-peak ratio is a useful measure of the persistence of antihypertensive efficacy at the end of the dosing interval. This ratio was found to be close to the ideal of 1.0 for candesartan cilexetil, 8 and 16 mg, whereas it was 0.7 for the prototype AT1-receptor blocker losartan, 50 mg. The antihypertensive effect of candesartan cilexetil, 16 mg, was also significantly greater than that of losartan, 100 mg, as demonstrated by ambulatory blood pressure measurements 0-36 h after dosing and by clinic measurements 48 h after dosing. By controlling blood pressure well beyond the normal dosing interval, candesartan cilexetil provides cardiovascular protection even in those patients who may occasionally miss doses.
流行病学证据表明，最佳血压控制需要采取能在24小时内持续且充分降低血压的策略。为了最大程度提高依从性，抗高血压药物还需要在每日一次方便给药剂量下具有良好的耐受性和有效性。新型血管紧张素II 1型（AT1）受体阻滞剂坎地沙坦与AT1受体紧密结合且解离缓慢，从而能对肾素-血管紧张素系统产生持久抑制作用。这可能解释了其显著的降压效果，该效果在24小时内可平稳维持。谷峰比值是衡量给药间隔末期降压效果持续性的一个有用指标。发现坎地沙坦酯8毫克和16毫克的该比值接近理想值1.0，而原型AT1受体阻滞剂氯沙坦50毫克的该比值为0.7。如给药后0至36小时的动态血压测量以及给药后48小时的门诊测量所示，坎地沙坦酯16毫克的降压效果也显著大于氯沙坦100毫克。通过在正常给药间隔之外很好地控制血压，坎地沙坦酯即使在那些可能偶尔漏服药物的患者中也能提供心血管保护。
