Formulation of long-acting nifedipine tablets influences the heart rate and sympathetic nervous system response in hypertensive patients
Formulation of long-acting nifedipine tablets influences the heart rate and sympathetic nervous system response in hypertensive patients
复制标题
DOI：
10.1111/j.1365-2125.2007.03082.x
复制
发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Toal, Corey B.
中科院分区：
文献类型：
--
作者：
Brown, Morris J.;Toal, Corey B.
目的短效和长效制剂对硝苯地平的血流动力学反应有所不同。然而，尽管后者在构成上存在显着差异，但尚未进行比较。我们为期 1 个月的随机交叉研究旨在比较 30 毫克渗透、恒释硝苯地平胃肠道治疗系统 (N-GITS) 与胶囊迷你片 Coacten XL。方法对 44 名年龄 63 +/- 7 岁的高血压患者进行了研究。在第15天和（单剂量）第30天更换配方。在第0、14、15、29和30天，给药后对患者进行6小时监测，在此期间测量血压（BP）、心率（HR）以及去甲肾上腺素（NE）和硝苯地平的血浆水平。主要结果是硝苯地平峰值水平时各制剂之间血浆 NE 的差异。 结果 第一次服用 Coacten 后，收缩压迅速下降，5 小时时达到最低点。 HR 上升 1.2 +/- 8.8 次分钟 (-1)。 N-GITS 后心率下降 2.4 +/- 7.7 次分钟(-1) (P = 0.159)。在硝苯地平浓度峰值时（分别为 4 小时和 5 小时），Coacten-治疗患者的血浆 NE（480 +/- 38.3 pg ml(-1)）高于 N-GITS 治疗患者（343 +/- 75.0 pg ml(-1)），并且它们相对于基线的变化显着不同（P = 0.0046）。在第 15 天和第 30 天，即转换配方后 5 小时，再次观察到药物之间的类似差异。结论这项研究表明，每日一次的硝苯地平的两种不同配方会导致不同的血压和血浆 NE 反应，并且配方之间的转换会对交感神经对血压下降的反应产生相反的影响。
AIMSThe haemodynamic responses to nifedipine vary between short- and long-acting formulations. However, the latter have not been compared despite marked differences in their constitution. Our 1-month randomized, crossover study was designed to compare the 30-mg osmotic, constant-release nifedipine gastrointestinal therapeutic system (N-GITS) with an encapsulated mini-tablet Coracten XL.METHODSForty-four hypertensive patients aged 63 +/- 7 years were studied. The formulation was changed on day 15 and (for a single dose) day 30. At days 0, 14, 15, 29 and 30, patients were monitored for 6 h after dosing, during which blood pressure (BP), heart rate (HR) and plasma levels of norepinephrine (NE) and nifedipine were measured. The primary outcome was the difference in plasma NE between formulations at the time of peak nifedipine level.RESULTSSystolic BP decreased rapidly after the first dose of Coracten, achieving nadir at 5 h. HR rose by 1.2 +/- 8.8 beats min(-1). After N-GITS HR fell by 2.4 +/- 7.7 beats min(-1) (P = 0.159). Plasma NE was higher in the Coracten- (480 +/- 38.3 pg ml(-1)) than N-GITS-treated patients (343 +/- 75.0 pg ml(-1)) at the time of peak nifedipine concentrations (4 and 5 h, respectively) and their change from baseline was significantly (P = 0.0046) different. A similar difference between the drugs was seen again at days 15 and 30, at 5 h after switching formulations.CONCLUSIONSThis study suggests that two different formulations of once-daily nifedipine result in different BP and plasma NE responses, and that switching between formulations causes opposite effects upon the sympathetic nervous response to falling BP.