Apnea of Prematurity, Caffeine, Premature Newborn
Conditions
Keywords
Infant, Premature, Caffeine, Pharmacokinetics, Metabolism
Brief summary
Almost all infants born \<29 weeks gestational age develop apnea of prematurity and are treated with caffeine. Type of diet and disease states may be significant contributors of variability in caffeine metabolism and pharmacokinetics (PK) in this population. This prospective, observational, open-label, opportunistic PK study will compare the population PK of caffeine between infants fed formula and infants fed exclusively breast milk; compare the activities of caffeine metabolizing enzymes between infants fed formula and infants fed exclusively breast milk; and determine the effect of hypoxia, hypotension, and infection on caffeine PK and metabolism in premature infants.
Detailed description
This study will use a consecutive patient sampling approach. All eligible participants admitted at each site will be approached. Caffeine and feedings will be administered per standard of care. Manipulations of caffeine dosing or feeding regimens will not be a part of this protocol. To minimize the amount of blood sampling, the investigators will use a sparse sampling methodology. Urine will be collected for analysis of caffeine and caffeine metabolite concentrations. Caffeine pharmacokinetics will be described by population pharmacokinetic analysis. Urinary concentrations of caffeine and its metabolites will be used to calculate metabolic ratios as markers of enzyme activity.
Interventions
DRUGCaffeine
Given per standard of care.
Sponsors
University of North Carolina, Chapel Hill
Duke University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 15 Days
Healthy volunteers
No
Inclusion criteria
* Written informed consent from parent(s) or legal guardian(s) * \<29 weeks birth gestational age * Postnatal age ≤15 days * Receiving caffeine (intravenous or oral) per standard of care for prevention or treatment of apnea of prematurity
Exclusion criteria
* Known major congenital or chromosomal anomaly
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clearance (CL) of caffeine at steady state | Study days 0, 15, 30, 45, and 60. | Using population pharmacokinetic analyses |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of distribution (V) of caffeine at steady state | Study days 0, 15, 30, 45, and 60 | Using population pharmacokinetic analyses |
| Caffeine metabolizing enzyme activity using urinary metabolic ratios | Study days 0, 15, 30, 45, and 60 | Activity levels of CYP1A2, xanthine oxidase, and N-acetyltransferase 2 |
| Fold change in caffeine clearance due to hypoxia, hypotension, and infections | Study days 0, 15, 30, 45, and 60 | Effect of hypoxia, hypotension, and infections on caffeine clearance |
Countries
United States
Outcome results
None listed