Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Y. A. Bijleveld, Raa Mathôt, J. H. van der Lee, F. Groenendaal, P. H. Dijk, A. van Heijst, Shp Simons, K. P. Dijkman, Hlm van Straaten, M. Rijken, I. A. Zonnenberg, F. Cools, A. Zecic, Dhgm Nuytemans, A. H. van Kaam, T. R. de Haan

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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
Issue number3
Early online date2017
Publication statusPublished - 1 Mar 2018

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