Effect of Feedings on Caffeine in Premature Infants

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effect of Feedings on Caffeine Pharmacokinetics and Metabolism in Premature Infants

Conditions
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Apnea of Prematurity, Premature Newborn, Caffeine

Intervention / Treatment
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* Drug: Caffeine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 15 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Premature infants<br>Premature infants <29 weeks birth gestational age receiving caffeine per standard of care for the prevention or treatment of apnea of prematurity. | Drug: Caffeine<br>* Given per standard of care.<br>* Other names: Cafcit;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance (CL) of caffeine at steady state | Using population pharmacokinetic analyses | Study days 0, 15, 30, 45, and 60. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Volume of distribution (V) of caffeine at steady state | Using population pharmacokinetic analyses | Study days 0, 15, 30, 45, and 60 | 
| Caffeine metabolizing enzyme activity using urinary metabolic ratios | Activity levels of CYP1A2, xanthine oxidase, and N-acetyltransferase 2 | Study days 0, 15, 30, 45, and 60 | 
| Fold change in caffeine clearance due to hypoxia, hypotension, and infections | Effect of hypoxia, hypotension, and infections on caffeine clearance | Study days 0, 15, 30, 45, and 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Infant, Premature, Caffeine, Pharmacokinetics, Metabolism