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Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns

Jacob V Aranda1, Kay D Beharry2

  • 1Division of Neonatology and the Neonatal Clinical and Translational Pharmacology Research Laboratory, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA; Professor of Pediatrics and Ophthalmology and Director of Neonatology PI/Director: New York Pediatric Developmental Pharmacology Research Consortium Program Director: Neonatal -Perinatal Medicine Fellowship State University of New York Downstate Medical Center, 450 Clarkson Avenue, Box 49 Brooklyn, New York City, NY, 11203, USA.

Seminars in Fetal & Neonatal Medicine
|December 9, 2020
PubMed

Insights

Caffeine has a long elimination half-life in newborns, with efficacy for apnea at low plasma levels. Higher doses may improve apnea control but increase complex, potentially toxic, pharmacodynamic effects.

Area of Science:

  • Neonatal Pharmacology
  • Respiratory Medicine

Background:

  • Caffeine is a widely used medication for neonatal apnea.
  • Neonates exhibit prolonged caffeine elimination half-lives (approx. 100 hours).
  • Caffeine demonstrates wide interindividual pharmacodynamic variability and a broad therapeutic index in preterm infants.

Purpose of the Study:

  • To review the pharmacokinetics and pharmacodynamics of caffeine in newborns.
  • To discuss the efficacy and safety thresholds of caffeine for neonatal apnea.

Main Methods:

  • Literature review of pharmacokinetic and pharmacodynamic studies on caffeine in neonates.
  • Analysis of reported plasma concentrations, efficacy, and toxicity data.

Main Results:

  • Caffeine is rapidly absorbed orally with complete bioavailability; dose adjustments are unnecessary when switching administration routes.
  • Efficacy for respiratory drive is observed at plasma levels around 2 mg/L via adenosine receptor inhibition.
  • Toxicity thresholds are ill-defined, potentially high (up to 60 mg/L), with complex actions at higher concentrations.

Conclusions:

  • Caffeine is effective for neonatal apnea, with a wide therapeutic index.
  • Higher doses may enhance apnea control but carry risks of complex and potentially toxic pharmacodynamic effects.
  • The influence of pharmacogenomic factors on neonatal caffeine response requires further investigation.

Keywords:
AdenosineApnea of prematurityCaffeineMetabolismMethylxanthinePharmacodynamicsPharmacokineticsPremature newborn

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