Logo image
Back
Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic-Ischemic Encephalopathy Receiving Controlled Hypothermia
Journal article   Peer reviewed

Population Pharmacokinetics of Gentamicin in Neonates with Hypoxemic-Ischemic Encephalopathy Receiving Controlled Hypothermia

Jeffrey J Cies, Thomas Habib, Vidhy Bains, Megan Young and Ogechukwu R Menkiti
Pharmacotherapy, v 38(11), pp 1120-1129
Nov 2018
DOI: https://doi.org/10.1002/phar.2186
PMID: 30300445
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Anti-Bacterial Agents - pharmacokinetics Birth Weight Computer Simulation Female Gentamicins - pharmacokinetics Humans Hypothermia, Induced Hypoxia-Ischemia, Brain - metabolism Hypoxia-Ischemia, Brain - therapy Infant, Newborn Male Monte Carlo Method Population Prospective Studies
Identify population pharmacokinetics and pharmacodynamic target attainment of gentamicin in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing controlled hypothermia (CH). Prospective open-label pharmacokinetic study. Gentamicin concentrations were modeled and dosing regimens simulated for a 5000-patient neonatal population with HIE receiving CH using PMetrics, a nonparametric, pharmacometric modeling, and simulation package for R. A 189-bed children's tertiary care teaching hospital. Twelve patients, 5 (42%) females and 7 (58%) males, met inclusion criteria with a median gestation age of 39.9 weeks (interquartile range [IQR] 38.5-40.2 wks) and a median birthweight (BW) of 3.3 kg (IQR 3.1-3.7 kg). Gentamicin concentrations were best described by a two-compartment model with first-order elimination with BW as a covariate on volume of distribution (Vd). The mean total body population clearance (CL) was 2.2 ± 0.7 ml/minute/kg, and the volume of the central compartment was 0.44 ± 0.06 L/kg. The R , bias, and precision for the observed versus population predicted model were 0.917, 1.15, and 10.9 μg/ml; the R , bias, and precision for the observed versus individual predicted model were 0.982, -0.132, and 0.932 μg/ml, respectively. The calculated mean population estimate for the total Vd was 0.96 ± 0.4 L/kg. The dosing regimen that most consistently produced a maximum concentration (C ) in the range of 10-12 mg/L with a minimum concentration (C ) level less than 2 mg/L was 5 mg/kg/dose given every 36 hours. These data suggest the population pharmacokinetics of gentamicin in neonates with HIE receiving CH have an increase in gentamicin CL and are different from previous reports in neonates with HIE not receiving CH and/or neonates without HIE. This analysis suggests a dosing regimen of 5 mg/kg/dose every 36 hours results in a gentamicin C within the range of 10-12 mg/L with a C lower than 2 mg/L, which is appropriate for treating susceptible gram-negative organisms with minimum inhibitory concentrations of 1 mg/L or lower.

Metrics

10 Record Views
9 citations in Web of Science
7 citations in Scopus

Details

UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

InCites Highlights

Data related to this publication, from InCites Benchmarking & Analytics tool:

Web of Science research areas
Pharmacology & Pharmacy
Logo image