Johnsson G, Murray G, Tweddel A, Hutton I
Eur J Clin Pharmacol. 1983;24(1):49-53. doi: 10.1007/BF00613926.
The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22-31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15 +/- 4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2 +/- 0.31/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33 +/- 5 ml and 23 +/- 3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23 +/- 3 ms) and an increase in the left ventricular ejection time (29 +/- 3 ms). The quotient PEP/LVET fell from 0.36 +/- 0.01 to 0.28 +/- 0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.
在8名年龄在22至31岁之间的健康男性受试者中研究了一种新型血管舒张药物非洛地平的血流动力学效应。该药物以0.15mg/kg的剂量制成口服溶液给药。35分钟后,再给予0.15mg/kg的剂量。非洛地平可使舒张压(最大效应为15±4mmHg)和全身血管阻力显著降低。心输出量增加(最大增加4.2±0.31/min),这是由于每搏输出量和心率均增加所致。每搏输出量(通过超声心动图测量)和心率的最大增加分别为33±5ml和23±3次/分钟。非洛地平可使射血前期显著缩短(23±3ms),左心室射血时间延长(29±3ms)。PEP/LVET比值从0.36±0.01降至0.28±0.01。当血浆水平约为15nmol/l时,可记录到非洛地平的显著活性。当记录到最大血流动力学效应时,血浆水平约为40nmol/l。累积剂量达到0.30mg/kg后,最大血浆水平有两倍的变化(从31至61nmol/l)。本研究结果与先前在动物身上进行的血流动力学研究一致。看来非洛地平是一种强效的小动脉血管舒张剂,在高血压或充血性心力衰竭患者的治疗中可能具有相当大的价值。