Protocol Deviation in Pharmacokinetics of Sildenafil in Premature Infants

Protocol Deviation data
Study Description
This was a phase I, open-label, pharmacokinetic (PK) study with a primary objective of determining PK of sildenafil in premature infants. The trial enrolled 25 premature infants ≤28 weeks gestational age (GA) who were receiving sildenafil per local standard of care at doses between 0.5-2.25 mg/kg in cohort 1, as well as 9 premature infants ≤28 weeks GA and postnatal age range 7-40 days who received a single intravenous dose of sildenafil 0.25 mg/kg or 0.125 mg/kg in cohort 2. A population PK model of sildenafil and metabolite N-desmethyl sildenafil (DMS) was developed. Fluconazole, a CYP3A4 inhibitor, was the only covariate found to explain a significant amount of the variability in sildenafil clearance. Although there is no widely accepted exposure target for sildenafil in the setting of bronchopulmonary dysplasia, simulated exposures obtained here are in agreement with previous population PK analysis performed in infants. Includes 25 enrolled premature infants who were receiving sildenafil per local standard of care in cohort 1, and 9 enrolled premature infants who received a single intravenous dose of sildenafil in cohort 2.