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Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia
Author(s) -
Bijleveld YA,
Mathôt RAA,
van der Lee JH,
Groenendaal F,
Dijk PH,
Heijst A,
Simons SHP,
Dijkman KP,
Straaten HLM,
Rijken M,
Zonnenberg IA,
Cools F,
Zecic A,
Nuytemans DHGM,
Kaam AH,
Haan TR
Publication year - 2018
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.748
Subject(s) - pharmacokinetics , volume of distribution , medicine , hypothermia , gestational age , urine , anesthesia , population , biology , pregnancy , environmental health , genetics
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.