Effects of Sildenafil on CFTR-dependent Ion Transport Activity

Exclusion Criteria

• •1. History of hypersensitivity to sildenafil
• •2. Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
• •3. Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study
• •4. History of significant hepatic (SGOT or SGPT \> 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), cardiovascular (history of aortic stenosis, coronary artery disease, pulmonary hypertension with right ventricular systolic pressure \>55 mmHg or life-threatening arrhythmia), neurological (history of stroke), hematologic (history of bleeding diathesis), ophthalmologic (history of retinal impairment or non-arteritic ischemic optic neuritis) or renal impairment (creatinine \>1.8 mg/dL.)
• •5. Inability to swallow pills
• •6. Previous lung transplantation
• •7. Use of concomitant nitrates, α-blocker, or Ca channel blocker
• •8. Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin, verapamil)
• •9. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data
• •10. Weight less than 40 kg
• •11. History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening
• •12. History of nasal disease or nasal surgery that would, in the opinion of the investigator, impede accurate measurements of NPD
• •13. Use of anticoagulant medication (e.g. heparin, coumadin)
• •14. Resting room air oxygen saturation \<93%
• •15. Use of nighttime oxygen
• •15\) History of migraine headaches 16) Baseline BP of \< 90/50 mm Hg