Hermida Ramón C, Calvo Carlos, Ayala Diana E, López José E, Rodríguez Marta, Chayán Luisa, Mojón Artemio, Fontao María J, Fernández José R
Bioengineering & Chronobiology Laboratories, University of Vigo, Vigo, Spain.
Chronobiol Int. 2007;24(3):471-93. doi: 10.1080/07420520701420683.
Previous chronotherapy studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium channel blockers (CCB), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the antihypertensive efficacy and safety profile of the slow-release, once-a-day nifedipine gastrointestinal therapeutic system (GITS) formulation administered at different times with reference to the rest-activity cycle of each participant. We studied 80 diurnally active subjects (36 men and 44 women), 52.1+/-10.7 yrs of age, with grade 1-2 essential hypertension, who were randomly assigned to receive nifedipine GITS (30 mg/day) as a monotherapy for eight weeks, either upon awakening in the morning or at bedtime at night. Patients with uncontrolled BP were up-titrated to a higher dose, 60 mg/day nifedipine GITS, for an additional eight weeks. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours before and after therapy with either dose. The BP reduction after eight weeks of therapy with the lower dose of 30 mg/day was slightly, but not significantly, larger with bedtime dosing. The efficacy of 60 mg/day nifedipine GITS in non-responders to the initial 30 mg/day dose was twice as great with bedtime as compared to morning dosing. Moreover, bedtime administration of nifedipine GITS reduced the incidence of edema as an adverse event by 91%, and the total number of all adverse events by 74% as compared to morning dosing (p=0.026). Independent of the time of day of administration, a single daily dose of 30 mg/day of nifedipine GITS provides full 24 h therapeutic coverage. The dose-dependent increased efficacy and the markedly improved safety profile of bedtime as compared to morning administration of nifedipine GITS should be taken into account when prescribing this CCB in the treatment of essential hypertension.
既往的时间治疗学研究表明，在早晨或晚上服用包括氨氯地平、伊拉地平、维拉帕米、尼群地平和西尼地平在内的几种钙通道阻滞剂（CCB）后，血压（BP）的昼夜模式保持不变。本试验参照每位参与者的休息-活动周期，研究了在不同时间给药的缓释、每日一次硝苯地平胃肠道治疗系统（GITS）制剂的降压疗效和安全性。我们研究了80名日间活动的受试者（36名男性和44名女性），年龄为52.1±10.7岁，患有1-2级原发性高血压，他们被随机分配接受硝苯地平GITS（30毫克/天）作为单一疗法治疗8周，要么在早晨醒来时服用，要么在晚上睡觉前服用。血压未得到控制的患者被加量至更高剂量，即60毫克/天的硝苯地平GITS，再治疗8周。在使用任一剂量治疗前后，连续48小时白天每20分钟、晚上每30分钟通过动态监测测量血压。使用30毫克/天的较低剂量治疗8周后，睡前给药的血压降低幅度略大，但无显著差异。对于初始30毫克/天剂量无反应的患者，60毫克/天硝苯地平GITS的疗效睡前给药是早晨给药的两倍。此外，与早晨给药相比，睡前服用硝苯地平GITS使水肿作为不良事件的发生率降低了91%，所有不良事件的总数降低了74%（p=0.026）。无论给药时间如何，每日单次剂量30毫克/天的硝苯地平GITS可提供完整的24小时治疗覆盖。在开具这种CCB治疗原发性高血压时，应考虑到与早晨给药相比，睡前给药硝苯地平GITS的剂量依赖性疗效增加和安全性显著改善。
