Document Detail


Efficacy and tolerability of the renin inhibitor Ro 42-5892 in patients with hypertension.
MedLine Citation:
PMID:  8222499     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The efficacy of multiple oral administration of the renin inhibitor Ro 42-5892 [(S)-alpha-](t-butylsulfonyl)-methyl]hydrocinnamamido]-N-[1S , 2R,3S)-1-(cyclohexylmethyl)-3-cyclopropyl-2,3-dihydroxypropyl]-imi dazole-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.
Authors:
G A Rongen; J W Lenders; C H Kleinbloesem; C Weber; H Welker; E Fahrner; H Pozenel; A J Woittiez; G Haug; M S Buchmann
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical pharmacology and therapeutics     Volume:  54     ISSN:  0009-9236     ISO Abbreviation:  Clin. Pharmacol. Ther.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1993-12-21     Completed Date:  1993-12-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372741     Medline TA:  Clin Pharmacol Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  567-77     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University Hospital Nijmegen, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Aged
Analysis of Variance
Antihypertensive Agents / adverse effects,  pharmacology,  therapeutic use*
Biological Availability
Blood Pressure / drug effects
Double-Blind Method
Female
Humans
Hypertension / drug therapy*
Imidazoles / adverse effects,  pharmacology,  therapeutic use*
Injections, Intravenous
Male
Middle Aged
Renin / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Imidazoles; 135669-48-6/remikiren; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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