Pharmacokinetic variability of caffeine in routinely treated preterm infants: Preliminary considerations on developmental changes of systemic clearance

Masato Taguchi*, Yukako Kawasaki, Arisa Katsuma, Ayane Mito, Kentaro Tamura, Masami Makimoto, Taketoshi Yoshida

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The purpose of this study was to clarify the variability of serum concentrations of caffeine (CAF) in preterm infants, and to deliberate on a better explanation for developmental changes of systemic clearance during the neonatal period. Forty-nine serum samples were obtained from 23 preterm neonates (age, 34.1±18.8d), and additive blood sampling was conducted periodically for 10 of the 23 patients after discontinuation of CAF treatment. The concentrations of CAF and its major metabolites were determined by liquid chromatography-tandem mass spectrometory. The serum concentrations of CAF were within therapeutic levels (5–25µg/mL) in 37 samples and exceeded 25µg/mL in the rest of the 12 samples, although no sample was in the toxic range (> 50µg/mL). The inter- and intra-individual variability of the concentration to dose (C/D) ratio corrected for body surface area (BSA) was more negatively associated with postmenstrual age (PMA) rather than postnatal age (PNA). The serum concentrations of major metabolites were much smaller than those of CAF throughout the study, suggesting that the contribution of hepatic metabolism to drug elimination was small in the preterm infants under 241d of PMA. The mean values for elimination half-life and oral clearance estimated in the 10 patients were 124.6±44.6h and 2.26±0.73mL/min/1.73m2, respectively. Consequently, we confirmed that the exposure to CAF was considerably variable and provided additive insight that the C/D ratio corrected for patient’s BSA and PMA are promising for describing and understanding the developmental change of clearance in preterm infants.

Original languageEnglish
Pages (from-to)69-74
Number of pages6
JournalBiological and Pharmaceutical Bulletin
Volume44
Issue number1
DOIs
StatePublished - 2021/01/01

Keywords

  • Caffeine
  • Gestational age
  • Pharmacokinetics
  • Postmenstrual age
  • Postnatal age
  • Preterm infant

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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