Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease.

Academic Article

Abstract

  • 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.
  • Authors

    Published In

    Keywords

  • Biomarkers, Cystic fibrosis, Inflammation, Pharmacokinetics, Phosphodiesterase inhibitors, Sildenafil, Adult, Biomarkers, Cystic Fibrosis, Drug Monitoring, Female, Humans, Inflammation, Leukocyte Elastase, Lung, Male, Phosphodiesterase 5 Inhibitors, Severity of Illness Index, Sildenafil Citrate, Sputum, Treatment Outcome
  • Digital Object Identifier (doi)

    Author List

  • Taylor-Cousar JL; Wiley C; Felton LA; St Clair C; Jones M; Curran-Everett D; Poch K; Nichols DP; Solomon GM; Saavedra MT
  • Start Page

  • 228
  • End Page

  • 236
  • Volume

  • 14
  • Issue

  • 2