Pranidipine, a novel calcium antagonist, once daily, for the treatment of hypertension: A multicenter, double-blind, placebo-controlled dose-finding study

摘要

The antihypertensive effects and tolerance of once-daily (od), pranidipine, a novel dihydopyridine derivative with a long duration of action, were evaluated in a double-blind, placebo-controlled, parallel-group dose-finding study. A total of 199 patients, with a diastolic blood pressure (BP) of 95–115 mmHg, were included in the trial. After 4 weeks on placebo, patients were randomly assigned to either placebo or pranidipine at 1, 2, 4, or 8 mg od for a further 4 weeks. A dose response was seen in the reduction (Δ) of diastolic BP: placebo, Δ1.7 mm Hg; 1 mg, Δ6.4 mmHg; 2 mg, Δ7.5 mmHg, p<0.01; 4 mg, Δ11.5 mmHg, p<0.01; and 8 mg, Δ10.6 mmHg, p<0.01. There were no meaningful changes in heart rate. The number of responders (decrease of diastolic blood pressure to<90 mmHgandby 10 mmHg or more from baseline value) in each group also revealed a dose-response relationship: placebo=9; 1 mg=25, n.s.; 2 mg=27, n.s.; 4 mg=41.5, p<0.01; and 8 mg=41, p<0.01 (compared with placebo). Plasma concentrations of pranidipine also demonstrated linear dose-response relationships. An increase in adverse events was observed within the 8 mg group. The degree of reduction in BP and the number of responders were not greater in the 8 mg group compared with the 4 mg group, although the plasma concentration (mean values, ng/dl) of pranidine in the 8 mg group was higher (2.2 on day 42; 2.3 on day 56) compared with the 4 mg group (1.4 on day 42; 1.6 on day 56). In conclusion, pranidipine is a well-tolerated and 24-hour effective novel calcium antagonist that reduces BP in a dose-related manner up to