Vulpis V, Seccia T M, Ricci S, Pirrelli A
DIMO, Sezione di Medicina Interna, Università degli Studi di Bari.
Riv Eur Sci Med Farmacol. 1993 Sep-Dec;15(5-6):227-35.
Aim of this study was to evaluate the antihypertensive efficacy, tolerability, drug plasma levels and hemodynamic effects after long-term treatment with the slow release (SR) formulation of verapamil (240 mg od). After a wash-out period of two weeks, 96 subjects (39 M, 57 F; mean age: 55 +/- 8.4 years; recruited in 9 centers) with mild to moderate, uncomplicated hypertension received verapamil 240 mg SR od for 24 weeks. The following parameters were considered: systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), ECG, echocardiogram, routine blood and urine chemistries, drug plasma levels. In addition, hemodynamic parameters were assessed in 30 subjects. A significant decrease in SBP and DBP (p < 0.01) was observed already after 1 week of treatment and was evident during all the study. HR was significantly reduced after 4 weeks (p < 0.01). No changes of ECG and echocardiographic parameters occurred. A significant increase in drug plasma levels was measured after 12 and 24 weeks of treatment (p < 0.05), when compared to the values recorded after 1 week. After 24 weeks drug levels were slightly decreases, even if not significantly, when compared to the values observed at the 12th week. No significant changes of cardiac output (CO), cardiac index (CI), stroke volume (SV) were evident. Total vascular resistances (TVR) decreases significantly (p < 0.001) 80 subjects completed the study. These results confirm the antihypertensive efficacy and tolerability of SR formulation of verapamil and suggest that the effective mechanism by which it reduces blood pressure is the progressive reduction of TVR without a sympathetic reflex stimulation. This hemodynamic effect is achieved by small drug concentrations. In conclusion, SR formulation of verapamil allows a good therapeutic control in hypertensive subjects when it is administered od and, therefore, it can be considered a drug of first choice in the treatment of arterial hypertension.
本研究的目的是评估维拉帕米缓释制剂（每日240毫克）长期治疗后的降压疗效、耐受性、药物血浆水平和血流动力学效应。在为期两周的洗脱期后，96名受试者（39名男性，57名女性；平均年龄：55±8.4岁；在9个中心招募）患有轻度至中度、无并发症的高血压，接受每日240毫克维拉帕米缓释制剂治疗24周。考虑了以下参数：收缩压（SBP）和舒张压（DBP）、心率（HR）、心电图、超声心动图、常规血液和尿液化学检查、药物血浆水平。此外，对30名受试者评估了血流动力学参数。治疗1周后即观察到SBP和DBP显著降低（p<0.01），且在整个研究过程中均很明显。4周后HR显著降低（p<0.01）。心电图和超声心动图参数无变化。与1周后记录的值相比，治疗12周和24周后药物血浆水平显著升高（p<0.05）。与第12周观察到的值相比，24周后药物水平略有下降，即使不显著。心输出量（CO）、心脏指数（CI）、每搏输出量（SV）无明显显著变化。总血管阻力（TVR）显著降低（p<0.001）。80名受试者完成了研究。这些结果证实了维拉帕米缓释制剂的降压疗效和耐受性，并表明其降低血压的有效机制是逐渐降低TVR而无交感反射刺激。这种血流动力学效应通过小剂量药物浓度即可实现。总之，维拉帕米缓释制剂每日给药时能在高血压患者中实现良好的治疗控制，因此可被视为治疗动脉高血压的首选药物。
