Pharmacokinetic studies of nifedipine tablet. Correlation with antihypertensive effects.
Pharmacokinetic studies of nifedipine tablet. Correlation with antihypertensive effects.
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硝苯地平片的药代动力学研究。
DOI：
10.1161/01.hyp.5.4_pt_2.ii29
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发表时间：
1983
期刊：
影响因子：
8.3
通讯作者：
P. Corvol
中科院分区：
文献类型：
--
作者：
A. Taburet;E. Singlas;J. Colin;O. Banzet;M. Thibonnier;P. Corvol
8名高血压住院男性（WHO I或II期，45 +/- 10岁）服用硝苯地平片剂。在首次安慰剂试验后，在一项单次给药双盲交叉研究中，于上午8点以随机顺序间隔72小时给予硝苯地平20、40和60 mg。由同一名观察员从上午7点至上午8点每20分钟测量两次血压和心率，然后每小时测量一次，直至晚上8点，首先患者躺下，站立1分钟后再次。从上午8点至中午每小时采集一次样品，从中午至下午8点每2小时采集一次样品，以及在药物摄入后24和48小时。这三种剂量都显著降低了血压。与20 mg给药后（7小时时为-11%）相比，60 mg给药后卧位期间的降低幅度显著更大（-18%），持续时间更长（12小时）。三种剂量引起心率相似的增加（+29%至+38%），最大值发生在第二小时，持续5小时。血浆峰浓度和血浆浓度-时间曲线下面积呈剂量依赖性;动力学在20 - 60 mg之间呈线性，硝苯地平片剂的半衰期接近10小时。平均动脉血压的降低与硝苯地平的血浆水平密切相关（r = 0.61; n = 190; p <0.001）。4名患者出现轻度副作用（头痛、潮红、嗜睡或虚弱）。硝苯地平的片剂形式具有有效的抗高血压作用，持续时间长于胶囊制剂。
A tablet form of nifedipine was given to eight hypertensive hospitalized men (Stage I or II WHO, 45 +/- 10 years old). After an initial placebo test, 20, 40, and 60 mg of nifedipine were given at 8.00 a.m. in random order at 72-hour intervals in a single administration double-blind crossover study. Blood pressure and heart rate were measured twice by the same observer every 20 minutes from 7.00 a.m. to 8.00 a.m. and then hourly until 8.00 p.m., first with the patients recumbent and again after 1 minute of standing. Plasma nifedipine levels were assayed in samples drawn hourly from 8.00 a.m. to noon, every 2 hours from noon to 8.00 p.m., and at 24 and 48 hours after drug ingestion. The three doses all lowered blood pressure significantly. The reduction during recumbency was significantly larger (-18%) and lasted longer (12 hours) after 60 mg than after 20 mg (-11% at 7 hours). The three doses caused similar increases in heart rate (+29% to +38%), the maximum occurring at the second hour and lasting for 5 hours. The peak plasma concentrations and areas under the plasma concentration time curve were dose-dependent; kinetics were linear between 20 and 60 mg, and the half-life of nifedipine tablets was close to 10 hours. The decrease in mean arterial blood pressure correlated strongly with plasma nifedipine levels (r = 0.61; n = 190; p less than 0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness, or weakness). The tablet form of nifedipine had a potent antihypertensive action that lasted longer than that of the capsule formulation.