| Entry-into-humans study with a new direct renin inhibitor. | |
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MedLine Citation:
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PMID: 22418829 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PURPOSE: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of escalating single oral doses of ACT-077825, a novel orally active renin inhibitor, in healthy male subjects. METHODS: In this single-center, double-blind, placebo- and active-controlled (with enalapril) randomized study, 70 subjects received a single dose of ACT-077825 (1-1,000 mg), placebo, or enalapril 20 mg under fasted conditions. The main pharmacokinetic endpoints were area under the plasma ACT-077825 concentration-time curve from time zero to infinity and the terminal half-life (t(1/2)). The pharmacodynamic endpoints included immunoactive active renin (iAR) plasma concentrations and plasma renin activity (PRA). Standard laboratory and safety data were collected. RESULTS: Of the few adverse events reported, diarrhea and headache were the most frequent. The pharmacokinetics of ACT-077825 were dose-proportional in the dose range 100 to 1,000 mg. Terminal t(1/2), best characterized following a dose of 1,000 mg, was 41.6 h and t(max) 4-5 h post-dose. ACT-077825 dose-dependently increased iAR and decreased PRA, effects that were associated with a decrease in blood pressure at 1,000 mg, similar to following treatment with enalapril. CONCLUSION: The results provide evidence that ACT-077825, with a pharmacokinetic profile consistent with a once-a-day dosing regimen, may represent an effective antihypertensive agent and pave the way toward a multiple-ascending dose study. |
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Authors:
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Laurent B Nicolas; Marcelo M Gutierrez; Christoph Binkert; Jasper Dingemanse |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-15 |
Journal Detail:
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Title: European journal of clinical pharmacology Volume: - ISSN: 1432-1041 ISO Abbreviation: - Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-3-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1256165 Medline TA: Eur J Clin Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Clinical Pharmacology, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123, Allschwil, Switzerland, laurent.nicolas@actelion.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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