Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Y. A. Bijleveld*, R. A.A. Mathôt, J. H. van der Lee, F. Groenendaal, P. H. Dijk, A. van Heijst, S. H.P. Simons, K. P. Dijkman, H. L.M. van Straaten, M. Rijken, I. A. Zonnenberg, F. Cools, A. Zecic, D. H.G.M. Nuytemans, A. H. van Kaam, T. R. de Haan

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.

Original languageEnglish
Pages (from-to)458-467
Number of pages10
JournalClinical Pharmacology and Therapeutics
Volume103
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018

Cite this

Bijleveld, Y. A., Mathôt, R. A. A., van der Lee, J. H., Groenendaal, F., Dijk, P. H., van Heijst, A., ... de Haan, T. R. (2018). Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia. Clinical Pharmacology and Therapeutics, 103(3), 458-467. https://doi.org/10.1002/cpt.748