Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery

The objective of this study was to characterize cefazolin serum pharmacokinetics in children before, during and after cardiopulmonary bypass (CPB), in order to derive an evidence-based dosing regimen. This study included children who received cefazolin before surgical incision, before cessation of C...

Full description

Saved in:
Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2017-03, Vol.72 (3), p.791-800
Main Authors: De Cock, Pieter A J G, Mulla, Hussain, Desmet, Sarah, De Somer, Filip, McWhinney, Brett C, Ungerer, Jacobus P J, Moerman, Annelies, Commeyne, Sabrina, Vande Walle, Johan, Francois, Katrien, Van Hasselt, Johan G C, De Paepe, Peter
Format: Article
Language:English
Subjects:
Adolescent
Anti-Bacterial Agents - administration & dosage
Anti-Bacterial Agents - blood
Anti-Bacterial Agents - pharmacokinetics
Antibiotic Prophylaxis
Cardiopulmonary Bypass
Cefazolin - administration & dosage
Cefazolin - blood
Cefazolin - pharmacokinetics
Child
Child, Preschool
Computer Simulation
Dose-Response Relationship, Drug
Female
Humans
Infant
Infant, Newborn
Male
Population
Prospective Studies
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The objective of this study was to characterize cefazolin serum pharmacokinetics in children before, during and after cardiopulmonary bypass (CPB), in order to derive an evidence-based dosing regimen. This study included children who received cefazolin before surgical incision, before cessation of CPB and after surgery. Blood samples of total and unbound cefazolin concentrations were collected before, during and after CPB. The cefazolin concentration-time profiles were analysed using population pharmacokinetic modelling and predictors for interindividual variability in pharmacokinetic parameters were investigated. Subsequently, optimized dosing regimens were developed using stochastic simulations. Clinicaltrials.gov: NCT02749981. A total of 494 total and unbound cefazolin concentrations obtained from 56 children (aged 6 days to 15 years) were included. A two-compartment model with first-order elimination plus an additional compartment for the effect of CPB best described the data. Clearance (1.56 L/h), central volume (1.93 L) and peripheral volume (2.39 L) were allometrically scaled by body weight. The estimated glomerular filtration rate (eGFR) was identified as a covariate on clearance and the serum albumin concentration was associated with maximum protein binding capacity. Our simulations showed that an additional bolus dose at the start of CPB improves the PTA in typical patients from 59% to >94%. Prolonged surgery and preserved renal function (i.e. drop in eGFR
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkw496