Safety and tolerability of bosentan in Idiopathic Pulmonary Fibrosis: open label study

¹ University of Giessen Lung Center - UGLC, Germany
² Pneumologische Klinik Waldhof Elgershausen, Greifenstein, Germany
³ Dept. of Internal Medicine, Klinikum Grosshadern, Ludwig-Maximilians-University Munich, Germany
⁴ Klinik Löwenstein, Löwenstein, Germany
⁵ Actelion Ltd, Allschwil, Switzerland

^* To whom correspondence should be addressed. E-mail: andreas.guenther{at}uglc.de.

	Abstract

Idiopathic Pulmonary Fibrosis (IPF) is a fatal disease, for which no effective treatment exists. Twelve IPF patients underwent analysis of gas exchange properties by the multiple inert gas elimination technique (MIGET) on day 1 before and after 125mg bosentan, a dual endothelin antagonist, followed by chronic administration for 12 weeks (62.5mg bid week 1, 125mg bid thereafter). Primary objective was the effect of bosentan on gas exchange (day 1) and on oxygen saturation and minute ventilation (week 2).

With one exception, where redistribution of total pulmonary blood flow from normal ventilation/perfusion (V_A/Q) areas (93% pre, 72% post) to low V_A/Q areas (0% pre, 22.2% post) was encountered, no patient showed any change in gas exchange (shunt flow 8.5±3.4% before, 6.1±2.3% after bosentan [% of cardiac output, mean±SD]; day1) or oxygen saturation and minute ventilation (week 2). Similarly, none of the secondary parameters was significantly changed at week 2 and at the end of the study period (week 12). 5 patients developed respiratory infections and 2 died because of pneumonia and this was judged as being unrelated to bosentan intake. In conclusion, bosentan administration seems not to induce clinically relevant gas exchange abnormalities in IPF patients.

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