Premium
Efficacy and tolerability of the renin inhibitor Ro 42‐5892 in patients with hypertension
Author(s) -
Rongen Gerard A,
Lenders Jacques W M,
Kleinbloesem Cees H,
Weber Cornelia,
Welker Horst,
Fahrner Eva,
Pozenel Hans,
Woittiez Arend Jan J,
Haug Gertraud,
Buchmann Marie S,
Höglund Christer E K,
Thien Theo
Publication year - 1993
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.1993.189
Subject(s) - blood pressure , medicine , placebo , tolerability , oral administration , renin inhibitor , plasma renin activity , anesthesia , renin–angiotensin system , adverse effect , alternative medicine , pathology
The efficacy of multiple oral administration of the renin inhibitor Ro 42‐5892 [(S)‐α‐[( t ‐butylsulfonyl)‐methyl]hydrocinnamamido] ‐N‐ [1S,2R,3S)‐1‐(cyclohexylmethyl)‐3‐cyclopropyl‐2,3‐dihydroxypropyl]‐imidazole‐4‐propionamide] was studied. Forty‐nine patients with moderate essential hypertension were randomly assigned to three groups that entered an 8‐day double‐blind oral treatment period: daily administration of placebo (group A), 300 mg Ro 42‐5892 (group B), or 600 mg Ro 42‐5892 (group C). Four hours after the last oral drug intake, placebo was administered intravenously to subjects in group A and 100 mg Ro 42‐5892 was administered intravenously to subjects in groups B and C. Sitting systolic and diastolic blood pressures were measured on days 1 and 8 with a blood pressure device. On day 1, systolic blood pressure maximally decreased by 13.3 ± 9.3, 20.2 ± 11.2, and 24.1 ± 11.3 mm Hg in groups A, B, and C, respectively (mean ± SD; p < 0.01 for group A versus group C). Diastolic blood pressure maximally decreased 9.4 ± 5.7, 13.9 ± 8.7, and 11.8 ± 5.7 mm Hg (difference not significant). On day 8, systolic blood pressure maximally decreased 19.5 ± 16.5, 26.5 ± 17.4, and 30.5 ± 18.4 mm Hg and diastolic blood pressure maximally decreased 14.8 ± 5.0, 16.2 ± 9.0, and 17.9 ± 12.7 mm Hg (difference not significant) compared with pretreatment values. Intravenous drug administration did not further reduce blood pressure, suggesting that the mode of action and not the low bioavailability was the limiting factor for the low efficacy. Clinical Pharmacology and Therapeutics (1993) 54, 567–577; doi: 10.1038/clpt.1993.189