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.

• Authors: J Rosenthal, N Hittel, K O Stumpe
• Journal: Cardiovascular drugs and therapy (Cardiovasc Drugs Ther) Vol. 10 Issue 1 Pg. 59-66 (Mar 1996) ISSN: 0920-3206 [Print] United States
• PMID: 8723171 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Calcium Channel Blockers
• Dihydropyridines
• pranidipine

Topics

• Adult
• Aged
• Calcium Channel Blockers (administration & dosage, adverse effects, blood)
• Dihydropyridines (administration & dosage, adverse effects, blood)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Hemodynamics (drug effects)
• Humans
• Hypertension (drug therapy)
• Male
• Middle Aged