Blood pressure and endocrine effects of single doses of CS-866, a novel angiotensin II antagonist, in salt-restricted hypertensive patients


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Article: article from journal or magazin.
Blood pressure and endocrine effects of single doses of CS-866, a novel angiotensin II antagonist, in salt-restricted hypertensive patients
Journal of Hypertension
Puchler  K., Nussberger  J., Laeis  P., Witte  P. U., Brunner  H. R.
0263-6352 (Print)
Publication state
Issued date
12 Pt 2
Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial --- Old month value: Dec
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.
Administration, Oral Adult Angiotensin II/*antagonists & inhibitors/blood 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 Receptors, Angiotensin/*antagonists & inhibitors Renin/blood Safety Tetrazoles/*administration & dosage/pharmacokinetics/therapeutic use Treatment Outcome
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05/03/2008 17:39
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20/08/2019 14:05
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