| Acute hemodynamic effects of single-dose sildenafil when added to established bosentan therapy in patients with pulmonary arterial hypertension: results of the COMPASS-1 study. | |
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MedLine Citation:
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PMID: 19755415 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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This study investigated the acute pharmacodynamic effects of sildenafil in patients with pulmonary arterial hypertension (PAH) and concomitant bosentan treatment, in view of a mutual pharmacokinetic interaction between the 2 drugs. This prospective, open-label, noncomparative, multicenter, phase II study enrolled 45 patients (>or=18 years) with stable PAH (idiopathic, familial, or related to corrected congenital systemic-to-pulmonary shunts, drugs, or toxins) and on bosentan treatment for at least 3 months. Patients underwent right heart catheterization to evaluate the acute hemodynamic effects of (a) inhaled nitric oxide (iNO) and (b) a single oral dose of sildenafil (25 mg). Mean pulmonary vascular resistance (PVR) decreased from baseline following iNO (-15%; 95% confidence limits: -21%, -8%; P = .0001). A statistically significant decrease from baseline in mean PVR was also observed 60 minutes following sildenafil administration (-15%; 95% confidence limits: -21%, -10%; P < .0001). The reduction in PVR following sildenafil was comparable to that resulting from iNO. There were no unexpected safety findings. The pharmacodynamic effect suggests that addition of sildenafil to bosentan treatment can elicit additional hemodynamic benefits. These data represent a rationale for long-term combination studies with the 2 compounds. |
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Authors:
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Ekkehard Gruenig; Evangelos Michelakis; Jean-Luc Vachi??ry; Carmine Dario Vizza; F Joachim Meyer; Martin Doelberg; Doris Bach; Jasper Dingemanse; Nazzareno Gali?? |
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Publication Detail:
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Type: Clinical Trial, Phase II; Journal Article; Multicenter Study Date: 2009-09-15 |
Journal Detail:
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Title: Journal of clinical pharmacology Volume: 49 ISSN: 1552-4604 ISO Abbreviation: J Clin Pharmacol Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-21 Completed Date: 2010-01-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0366372 Medline TA: J Clin Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 1343-52 Citation Subset: IM |
Affiliation:
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University Hospital, Heidelberg, Germany. ekkehard.gruenig@thoraxklinik-heidelberg.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antihypertensive Agents
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administration & dosage Drug Interactions Female Hemodynamics / drug effects* Humans Hypertension, Pulmonary / drug therapy Male Middle Aged Models, Cardiovascular Nitric Oxide / pharmacology Piperazines / administration & dosage, pharmacology* Pulmonary Artery / drug effects* Purines / administration & dosage, pharmacology Sulfonamides / administration & dosage* Sulfones / administration & dosage, pharmacology* Vasodilator Agents / administration & dosage, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Antihypertensive Agents; 0/Piperazines; 0/Purines; 0/Sulfonamides; 0/Sulfones; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 139755-83-2/sildenafil; 147536-97-8/bosentan |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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