title: Safety and tolerability of bosentan in idiopathic pulmonary fibrosis: an open label study.
abstract: Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which no effective treatment exists. In the present study, 12 IPF patients underwent analysis of gas exchange properties using the multiple inert gas elimination technique on day 1 before and after the administration of 125 mg bosentan, a dual endothelin antagonist. Following this, patients received chronic administration for 12 weeks (62.5 mg b.i.d. in week 1, 125 mg b.i.d. thereafter). The primary objective was to determine 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'/Q') areas (93% before, 72% after bosentan) to low V'/Q' areas (0% before, 22.2% after) was encountered, no patient showed any change in gas exchange (mean+/-SD shunt flow (% of cardiac output) 8.5+/-3.4% before, 6.1+/-2.3% after bosentan; day 1) or oxygen saturation and minute ventilation (week 2). Similarly, none of the secondary parameters was significantly changed either at week 2 or at the end of the study period (week 12). Five patients developed respiratory infections and two died because of pneumonia; this was judged as being unrelated to bosentan intake. In conclusion, bosentan administration does not seem to induce clinically relevant gas exchange abnormalities in idiopathic pulmonary fibrosis patients.
authors.affiliation: University of Giessen Lung Center - UGLC, Klinikstr. 36, D-35392 Giessen, Germany. andreas.guenther@uglc.de
authors.forename: A
authors.initials: A
authors.lastname: Günther
authors.forename: B
authors.initials: B
authors.lastname: Enke
authors.forename: P
authors.initials: P
authors.lastname: Markart
authors.forename: P
authors.initials: P
authors.lastname: Hammerl
authors.forename: H
authors.initials: H
authors.lastname: Morr
authors.forename: J
authors.initials: J
authors.lastname: Behr
authors.forename: G
authors.initials: G
authors.lastname: Stähler
authors.forename: W
authors.initials: W
authors.lastname: Seeger
authors.forename: F
authors.initials: F
authors.lastname: Grimminger
authors.forename: I
authors.initials: I
authors.lastname: Leconte
authors.forename: S
authors.initials: S
authors.lastname: Roux
authors.forename: H-A
authors.initials: HA
authors.lastname: Ghofrani
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D006328:Cardiac Catheterization; D016232:Endothelins / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000188:drug therapy*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D016232:Endothelins; D013449:Sulfonamides; D009569:Nitric Oxide; D000077300:Bosentan