[Plasma levels and noninvasive hemodynamic profile of slow release verapamil (240 mg). A multicenter study]

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.