Apnea of prematurity and caffeine pharmacokinetics: potential impact on hospital discharge

J Perinatol. 2016 Feb;36(2):141-4. doi: 10.1038/jp.2015.167. Epub 2015 Nov 12.


Objective: To determine the half-life of serum caffeine concentrations and its relation to apnea of prematurity (AOP) after caffeine is discontinued in preparation for hospital discharge.

Study design: Prospective cohort study involving preterm infants with gestational ages ⩽33 weeks at birth. After caffeine was discontinued, serum caffeine concentrations and electronic detection of pathologic apnea, defined a priori, were obtained at 24 and 168 h, respectively.

Result: Caffeine levels decreased from 13.3±3.8 to 4.3±2 mg l(-1) (n=50, mean±s.d.) at 24 and 168 h, respectively (P<0.01). The mean caffeine half-life was 87±25 h at 35±1 weeks postmenstrual age. Seven days after discontinuation of caffeine, 64% of the infants had pathologic apnea.

Conclusion: Hospital discharge planning for preterm infants with a history of AOP should be carefully considered after discontinuing caffeine. This study showed that caffeine may not reach subtherapeutic levels until around 11-12 days.

Publication types

  • Pragmatic Clinical Trial

MeSH terms

  • Apnea* / diagnosis
  • Apnea* / etiology
  • Apnea* / prevention & control
  • Caffeine* / administration & dosage
  • Caffeine* / blood
  • Caffeine* / pharmacokinetics
  • Drug Monitoring / methods
  • Female
  • Gestational Age
  • Half-Life
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / therapy*
  • Infant, Premature*
  • Male
  • Outcome Assessment, Health Care
  • Patient Discharge / standards
  • Purinergic P1 Receptor Antagonists / administration & dosage
  • Purinergic P1 Receptor Antagonists / blood
  • Purinergic P1 Receptor Antagonists / pharmacokinetics
  • Time Factors
  • Withholding Treatment / standards


  • Purinergic P1 Receptor Antagonists
  • Caffeine