Safety and tolerability of inhaled heparin in idiopathic pulmonary fibrosis

Journal of Aerosol Medicine and Pulmonary Drug Delivery
Philipp MarkartAndreas Guenther

Abstract

Abnormalities in alveolar coagulation occur in idiopathic pulmonary fibrosis (IPF). Anticoagulants attenuate bleomycin-induced lung fibrosis in animals. In this study, we first examined the pharmacokinetics of inhaled heparin in healthy subjects. Second, we investigated the safety and tolerability of heparin inhalation in IPF patients. Coagulation assays were performed in blood and bronchoalveolar lavage fluid samples from 19 healthy volunteers after inhalation of increasing amounts of unfractionated heparin. The acute effects of heparin inhalation on lung function and exercise capacity and the safety and tolerability of chronic heparin inhalation for 28 days were assessed in 20 IPF patients in an open-label exploratory pilot study. In healthy subjects, inhalation of 150,000 IU heparin ("filled dose") significantly increased the partial thromboplastin time and anti-factor Xa activity in blood samples indicating the threshold dose. The local alveolar anticoagulant effect was detectable up to 72 h, and the alveolar half-life was estimated at 28 h. In IPF-patients, no acute deleterious effects on pulmonary function, gas exchange, or exercise capacity were noted after inhalation of the threshold dose. During chronic treatment, wher...Continue Reading

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Methods Mentioned

BETA
bronchoalveolar
lavage
biopsy
pregnancy test
bronchoalveolar lavage
X–ray

Software Mentioned

AKITA
PharmaCalc
EuroQol

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