Population pharmacokinetic study of gentamicin: A retrospective analysis in a large cohort of neonate patients

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serval:BIB_39F2DCB21916
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
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Publications
Institution
Title
Population pharmacokinetic study of gentamicin: A retrospective analysis in a large cohort of neonate patients
Title of the conference
22nd Population Approach Group in Europe (PAGE) Meeting
Author(s)
Fuchs A., Guidi M., Giannoni E., Buclin T., Widmer N., Csajka C.
Address
Glasgow, Scotland, June 11-14, 2013
ISSN
1871-6032
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
22
Series
PAGE. Abstracts of the Annual Meeting of the Population Approach Group in Europe
Pages
Abstr. 2906
Language
english
Abstract
Objectives: Gentamicin is one of the most commonly prescribed antibiotics for suspected or proven infection in newborns. Because of age-associated (pre- and post- natal) changes in body composition and organ function, large interindividual variability in gentamicin drug levels exists, thus requiring a close monitoring of this drug due to its narrow therapeutic index. We aimed to investigate clinical and demographic factors influencing gentamicin pharmacokinetics (PK) in a large cohort of unselected newborns and to explore optimal regimen based on simulation.
Methods: All gentamicin concentration data from newborns treated at the University Hospital Center of Lausanne between December 2006 and October 2011 were retrieved. Gentamicin concentrations were measured within the frame of a routine therapeutic drug monitoring program, in which 2 concentrations (at 1h and 12h) are systematically collected after the first administered dose, and a few additional concentrations are sampled along the treatment course. A population PK analysis was performed by comparing various structural models, and the effect of clinical and demographic factors on gentamicin disposition was explored using NONMEM®.
Results: A total of 3039 concentrations collected in 994 preterm (median gestational age 32.3 weeks, range 24.2-36.5 weeks) and 455 term newborns were used in the analysis. Most of the data (86%) were sampled after the first dose (C1 h and C12 h). A two-compartment model best characterized gentamicin PK. Average clearance (CL) was 0.044 L/h/kg (CV 25%), central volume of distribution (Vc) 0.442 L/kg (CV 18%), intercompartmental clearance (Q) 0.040 L/h/kg and peripheral volume of distribution (Vp) 0.122 L/kg. Body weight, gestational age and postnatal age positively influenced CL. The use of both gestational age and postnatal age better predicted CL than postmenstrual age alone. CL was affected by dopamine and furosemide administration and non-significantly by indometacin. Body weight, gestational age and dopamine coadminstration significantly influenced Vc. Model based simulation confirms that preterm infants need higher dose, superior to 4 mg/kg, and extended interval dosage regimen to achieve adequate concentration.
Conclusions: This study, performed on a very large cohort of neonates, identified important factors influencing gentamicin PK. The model will serve to elaborate a Bayesian tool for dosage individualization based on a single measurement.
Create date
11/06/2013 10:12
Last modification date
31/01/2023 6:54
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