Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia
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.
|Persistent URL||dx.doi.org/10.1002/cpt.748, hdl.handle.net/1765/102402|
|Journal||Clinical Pharmacology and Therapeutics|
Bijleveld, Y, Mathot, R.A, van der Lee, J.H, Groenendaal, F, Dijk, P.H, van Heijst, A.F.J, … de Haan, T.R. (2017). Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia. Clinical Pharmacology and Therapeutics. doi:10.1002/cpt.748