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.

Abstract

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.

• Authors: Ekkehard Gruenig, Evangelos Michelakis, Jean-Luc Vachiéry, Carmine Dario Vizza, F Joachim Meyer, Martin Doelberg, Doris Bach, Jasper Dingemanse, Nazzareno Galiè
• Journal: Journal of clinical pharmacology (J Clin Pharmacol) Vol. 49 Issue 11 Pg. 1343-52 (Nov 2009) ISSN: 1552-4604 [Electronic] England
• PMID: 19755415 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antihypertensive Agents
• Piperazines
• Purines
• Sulfonamides
• Sulfones
• Vasodilator Agents
• Nitric Oxide
• Sildenafil Citrate
• Bosentan

Topics

• Antihypertensive Agents (administration & dosage)
• Bosentan
• 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)
• Sildenafil Citrate
• Sulfonamides (administration & dosage)
• Sulfones (administration & dosage, pharmacology)
• Vasodilator Agents (administration & dosage, pharmacology)