Pharmacokinetics of Sildenafil in Premature Infants

Phase 1

Completed

Brief Summary: The purpose of this study is to learn more about the safety and dosing of sildenafil in infants.

Detailed Description: Pharmacokinetics and safety of sildenafil will be studied in preterm infants who are receiving sildenafil per standard of care or 1 dose prescribed for the study.

Recruitment & Eligibility

Inclusion Criteria

Cohort 1:

Gestational age 28 weeks or less receiving sildenafil as standard of care < 365 postnatal days

Cohort 2:

Gestational age 28 weeks or less
7-28 postnatal days of age
Mechanical ventilation or nasal continuous positive airway pressure (NCPAP) or high-flow nasal cannula
Intravenous line in place

Exclusion Criteria

Cohort 1:

Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study

Cohort 2:

Previous exposure to sildenafil within 7 days prior to enrollment
Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
History of allergic reactions to sildenafil
AST > ULN or ALT > 3x ULN
Currently on a vasopressor for hypotension
Known sickle cell disease

Arm && Interventions

Group	Intervention	Description
sildenafil administered for study	1 dose of sildenafil	1 dose of sildenafil administered for study

Primary Outcome Measures

Name	Time	Method
Area under the plasma concentration versus time curve 0-24 hours for sildenafil	IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
Peak plasma concentration of sildenafil	IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
Clearance of sildenafil	IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
Volume of distribution at steady state	IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose
Half life of sildenafil	IV study dose 0-15 min,1-2,3-4,12-14,24-30,48-56hr after flush.Clinical care: IV <0.5hr before dose <15 min & 3-4hr after flush <0.5hr before next dose. Enteral <0.5hr before dose, 1-2 & 3-4hr after dose, <0.5hr before next dose. 22-26hr after last dose

Secondary Outcome Measures

Name	Time	Method
Evaluate P450 single nucleotide polymorphisms (SNPs)	2-7 days
Number of subjects with adverse events as a measure of safety and tolerability.	From the time of the first dose to 3 days after the last dose; serious adverse events will be collected from the first dose of sildenafil to 7 days after the last dose of sildenafil
Correlation between serum and dried blood spot samples	1-7 days

Locations (9): Riley Hospital
🇺🇸
Indianapolis, Indiana, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Kosair Pediatric Research Unit
🇺🇸
Louisville, Kentucky, United States
Albany Medical Center
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Albany, New York, United States
Kings County Hospital Center/SUNY Downstate Medical Center
🇺🇸
Brooklyn, New York, United States
Cincinnati Children's Hospital Medical Center
🇺🇸
Cincinnati, Ohio, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Duke University
🇺🇸
Durham, North Carolina, United States
Medical University of South Carolina
🇺🇸
Charleston, South Carolina, United States