Blood pressure and endocrine effects of single doses of CS-866, a novel angiotensin II antagonist, in salt-restricted hypertensive patients
| Autor: | Peter U. Witte, Jürg Nussberger, Hans R. Brunner, Kurt Püchler, Petra Laeis |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Male medicine.medical_specialty Ambulatory blood pressure Physiology Radioimmunoassay Administration Oral Tetrazoles Blood Pressure Plasma renin activity Angiotensin Receptor Antagonists Double-Blind Method Internal medicine Renin–angiotensin system Blood plasma Renin Internal Medicine Medicine Humans Active metabolite Cross-Over Studies Olmesartan Medoxomil Dose-Response Relationship Drug business.industry Angiotensin II Antagonist Imidazoles Blood Pressure Monitoring Ambulatory Diet Sodium-Restricted Middle Aged Blood pressure Endocrinology Treatment Outcome Hypertension Female Safety Cardiology and Cardiovascular Medicine business Follow-Up Studies |
| Zdroj: | Journal of hypertension. 15(12 Pt 2) |
| ISSN: | 0263-6352 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|