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

J Cyst Fibros. 2015 Mar;14(2):228-36. doi: 10.1016/j.jcf.2014.10.006. Epub 2014 Nov 13.


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: NCT00659529.

Keywords: Biomarkers; Cystic fibrosis; Inflammation; Pharmacokinetics; Phosphodiesterase inhibitors; Sildenafil.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / metabolism
  • Cystic Fibrosis* / physiopathology
  • Drug Monitoring / methods
  • Female
  • Humans
  • Inflammation / drug therapy
  • Leukocyte Elastase / metabolism*
  • Lung / metabolism
  • Lung / physiopathology
  • Male
  • Phosphodiesterase 5 Inhibitors / administration & dosage
  • Phosphodiesterase 5 Inhibitors / adverse effects
  • Phosphodiesterase 5 Inhibitors / pharmacokinetics
  • Severity of Illness Index
  • Sildenafil Citrate* / administration & dosage
  • Sildenafil Citrate* / adverse effects
  • Sildenafil Citrate* / pharmacokinetics
  • Sputum / drug effects*
  • Sputum / metabolism
  • Treatment Outcome


  • Biomarkers
  • Phosphodiesterase 5 Inhibitors
  • Sildenafil Citrate
  • Leukocyte Elastase

Associated data