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

Abstract

The antihypertensive effects and tolerance of once-daily (od), pranidipine, a novel dihydropyridine 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 (delta) of diastolic BP: placebo, delta 1.7 mm Hg; 1 mg, delta 6.4 mmHg; 2 mg, delta 7.5 mmHg, p < 0.01; 4 mg, delta 11.5 mmHg, p < 0.01; and 8 mg, delta 10.6 mmHg, p < 0.01. There were no meaningful changes in heart rate. The number of responders (decrease of diastolic blood pressure to < 90 mmHg and by 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 4 mg od.

Comparative Effects of Pranidipine with Amlodipine in Rats with Heart Failure

“…The dose of amlodipine they used was 20-100 times greater than that of pranidipine. Several other studies have demonstrated that amlodipine (2.5-10 mg/day) and pranidipine (1-4 mg/day) provided a consistent antihypertensive effect in a larger proportion of patients with hypertension [28][29][30] . Previously, we reported that pranidipine (0.3 mg/kg) improved cardiac function in rats with heart failure [14] .…”

Long-acting calcium channel antagonist pranidipine prevents ventricular remodeling after myocardial infarction in rats

“…This type of calcium channel antagonist appears to have fewer negative inotropic effects than earlier short-acting calcium channel antagonists [11][12][13]. Pranidipine is a similar type of long-acting calcium channel antagonist, which also has other pharmacological properties such as venodilator effects [14][15][16]. However, it is still unclear whether pranidipine prevents ventricular remodeling and progressive cardiac dysfunction in ischemic heart disease.…”