Document Detail


Blood pressure and endocrine effects of single doses of CS-866, a novel angiotensin II antagonist, in salt-restricted hypertensive patients.
MedLine Citation:
PMID:  9488244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: This study was conducted to assess the dose-response relationship of the new angiotensin II (Ang II) antagonist CS-866 on blood pressure and on endocrine parameters in hypertensive patients with an activated renin-angiotensin system.
DESIGN: Following a four-way crossover protocol, two groups of eight patients with mild-to-moderate hypertension received a sodium-restricted diet (60 mmol daily) and ingested single doses of 2.5, 10 and 40 mg or 5, 20 and 80 mg of CS-866, respectively, or placebo. Twenty-four hour ambulatory blood pressure measurements, plasma renin activity (PRA), Ang II and concentrations of RNH-6270, the pharmacologically active metabolite of CS-866, were monitored up to 24 h after medication.
RESULTS: CS-866 was well tolerated. There was a significant decrease in 24 h diastolic blood pressure (DBP) at all doses of CS-866 above 5 mg. Increasing doses of CS-866 from 2.5 to 10 mg and from 5 to 20 mg lowered the mean 24 h DBP and DBP AUC(0-24h) values considerably more than increasing doses from 10 to 40 mg and from 20 to 80 mg, respectively. The mean 24 h DBP was lowered by 6.9 and 8.4 mmHg after oral doses of 10 and 20 mg CS-866, respectively, compared with placebo and by 8.9 mmHg after 80 mg CS-866. The drug increased PRA and Ang II concentrations in plasma, maximum concentrations of which occurred within 3 h post-dose. The highest RNH-6270 concentrations were also found at the first post-dose measurement 3 h after administration of CS-866.
CONCLUSION: The new Ang II receptor antagonist CS-866 is effective and well tolerated. In salt-restricted hypertensive patients, CS-866 lowered blood pressure and increased PRA and Ang II concentrations at low doses. A single oral dose of 10-20 mg CS-866 resulted in almost maximal effects.
Authors:
K Püchler; J Nussberger; P Laeis; P U Witte; H R Brunner
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Journal of hypertension     Volume:  15     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1998-04-02     Completed Date:  1998-04-02     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  1809-12     Citation Subset:  IM    
Affiliation:
Sankyo Europe GmbH, Düsseldorf, Germany.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Adult
Angiotensin II / antagonists & inhibitors*,  blood
Angiotensin Receptor Antagonists*
Blood Pressure / drug effects*,  physiology
Blood Pressure Monitoring, Ambulatory
Cross-Over Studies
Diet, Sodium-Restricted*
Dose-Response Relationship, Drug
Double-Blind Method
Female
Follow-Up Studies
Humans
Hypertension / blood,  diet therapy,  drug therapy*
Imidazoles / administration & dosage*,  pharmacokinetics,  therapeutic use
Male
Middle Aged
Radioimmunoassay
Renin / blood
Safety
Tetrazoles / administration & dosage*,  pharmacokinetics,  therapeutic use
Treatment Outcome
Chemical
Reg. No./Substance:
0/Angiotensin Receptor Antagonists; 0/Imidazoles; 0/Tetrazoles; 11128-99-7/Angiotensin II; 6M97XTV3HD/olmesartan medoxomil; EC 3.4.23.15/Renin

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


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