Effect of feedings on caffeine pharmacokinetics in premature infants
Lawrence Ku, MD
BACKGROUND: Nearly all premature infants born at <29 weeks gestational age have apnea of prematurity and are treated with caffeine. Current caffeine dosing regimens result in widely varying systemic exposures, necessitating frequent monitoring and dose adjustments to maintain clinical effectiveness and prevent toxicity.
GAP: Prior studies suggest that infant formula enhances the metabolism of caffeine compared to breast milk. However, diet-induced differences in caffeine pharmacokinetics and metabolism remain poorly characterized in premature infants.
HYPOTHESIS: Premature infants fed formula will have lower caffeine plasma concentrations, experience more episodes of apnea, and require more dose escalations than infants fed breast milk. Infants fed formula will have higher caffeine clearances and increased concentrations of urinary caffeine metabolites compared to infants fed breast milk.
METHODS: We will retrospectively compare caffeine dosing, caffeine plasma concentrations, and clinical data between infants fed formula and infants fed breast milk who were <29 weeks gestation. We will conduct a prospective, multicenter, open-label, opportunistic pharmacokinetic study comparing infants fed formula and infants fed breast milk who are <29 weeks gestation and treated with caffeine for apnea of prematurity.
IMPACT: Quantifying the effect of diet on caffeine pharmacokinetics will help optimize caffeine dosing and improve the chances of successful therapy while reducing the risk of toxicity. Evaluating the effect of diet on caffeine metabolism will support future research identifying the constituents in diet responsible for these effects and determining how these factors might affect dosing of other drugs with similar metabolic properties.