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Hemodynamic and humoral effects of the novel calcium antagonist Ro 40‐5967 in patients with hypertension
Author(s) -
Schmitt Rita,
Kleinbloesem Cornells H,
Belz Gustav G,
Schroeter Volkmar,
Feifel Ulrich,
Pozenel Hans,
Kirch Wilhelm,
Halabi Atef,
Woittiez ArendJan J,
Welker Horst A,
Van Brummelen Peter
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.147
Subject(s) - blood pressure , medicine , hemodynamics , supine position , bradycardia , heart rate , plasma renin activity , antagonist , anesthesia , tolerability , placebo , endocrinology , renin–angiotensin system , adverse effect , receptor , alternative medicine , pathology
The tolerability and hemodynamic and humoral effects of the structurally novel calcium antagonist Ro 40‐5967 were investigated in 64 patients with hypertension. In a double‐blind, placebo‐controlled study, ascending oral doses of 50, 100, 150, or 200 mg were administered once daily for 8 days in a solution. Ro 40‐5967 was well tolerated up to 150 mg, but treatment was stopped in one patient in the 200 mg group because of bradycardia. Blood pressure was dose‐dependently reduced over the full 24‐hour dosing period with more pronounced effects on day 8 than on day 1. The maximum blood pressure reduction was obtained after 150 mg (supine blood pressure, −34/−25 mm Hg, p < 0.001). Despite a slight decrease in supine heart rate, cardiac output increased. PQ time was dose‐dependently increased and concentration‐effect analysis showed that relevant atrioventricular conduction disturbances occur only at concentrations much higher than those required to reduce blood pressure. Changes in catecholamines, plasma renin activity, and aldosterone were small and inconsistent. In conclusion, Ro 40‐5967 has a long‐lasting antihypertensive effect after once‐daily administration. Clinical Pharmacology and Therapeutics (1992) 52 , 314–323; doi: 10.1038/clpt.1992.147