Rationale: Airway inflammation is central to cystic fibrosis (CF) pathophysiology. Pre-clinical models have shown that phosphodiesterase inhibitors (PDEi) like sildenafil have anti-inflammatory activity. PDEi have not been studied in CF subjects.
Objectives: We evaluated the pharmacokinetics, tolerability, and safety of sildenafil in subjects with CF. Sputum biomarkers were used to explore efficacy.
Methods: An open-label pilot study of oral sildenafil administration was conducted in adults with mild to moderate CF lung disease. Subjects received oral sildenafil 20 or 40 mg p.o. t.i.d. for 6 weeks.
Measurements and main results: Twenty subjects completed the study. Estimated elimination rate constants were statistically different in subjects with CF compared to previously published non-CF subjects. Side effects were generally mild. There were no drug-related serious adverse events. Sputum neutrophil elastase activity decreased.
Conclusions: Subjects with CF may eliminate sildenafil at a faster rate than non-CF subjects. Sildenafil administration was safe in subjects with CF and decreased sputum elastase activity. Sildenafil warrants further study as an anti-inflammatory in CF.
Trial registration: ClinicalTrials.gov NCT00659529.
Keywords: Biomarkers; Cystic fibrosis; Inflammation; Pharmacokinetics; Phosphodiesterase inhibitors; Sildenafil.
Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.