title: Pharmacokinetics and tolerability of oral sildenafil in adults with cystic fibrosis lung disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States; Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States. Electronic address: Taylor-CousarJ@NJHealth.org.
authors.forename: J L
authors.initials: JL
authors.lastname: Taylor-Cousar
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States.
authors.forename: C
authors.initials: C
authors.lastname: Wiley
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico, Albuquerque, NM, United States.
authors.forename: L A
authors.initials: LA
authors.lastname: Felton
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.
authors.forename: C
authors.initials: C
authors.lastname: St Clair
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.affiliation: Division of Biostatistics and Bioinformatics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States; Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Denver, Denver, CO 80262, United States.
authors.forename: D
authors.initials: D
authors.lastname: Curran-Everett
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.
authors.forename: K
authors.initials: K
authors.lastname: Poch
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States; Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.
authors.forename: D P
authors.initials: DP
authors.lastname: Nichols
authors.affiliation: Internal Medicine, University of Alabama, 1720 2nd Ave South, Birmingham, AL 35294, United States.
authors.forename: G M
authors.initials: GM
authors.lastname: Solomon
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.
authors.forename: M T
authors.initials: MT
authors.lastname: Saavedra
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, 13123 E 16th Ave, Aurora, CO 80045, United States.
authors.forename: F J
authors.initials: FJ
authors.lastname: Accurso
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, United States.
authors.forename: J A
authors.initials: JA
authors.lastname: Nick
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019272:Leukocyte Elastase / Q000378:metabolism*; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012720:Severity of Illness Index; D000068677:Sildenafil Citrate / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D013183:Sputum / Q000187:drug effects* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D058986:Phosphodiesterase 5 Inhibitors; D000068677:Sildenafil Citrate; D019272:Leukocyte Elastase
keywords: Biomarkers; Cystic fibrosis; Inflammation; Pharmacokinetics; Phosphodiesterase inhibitors; Sildenafil