Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates.

Détails

ID Serval
serval:BIB_44A869ECA1E5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates.
Périodique
British Journal of Clinical Pharmacology
Auteur(s)
Fuchs A., Guidi M., Giannoni E., Werner D., Buclin T., Widmer N., Csajka C.
ISSN
1365-2125 (Electronic)
ISSN-L
0306-5251
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
78
Numéro
5
Pages
1090-1101
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
AIM: This study aims to investigate the clinical and demographic factors influencing gentamicin pharmacokinetics in a large cohort of unselected premature and term newborns and to evaluate optimal regimens in this population.
METHODS: All gentamicin concentration data, along with clinical and demographic characteristics, were retrieved from medical charts in a Neonatal Intensive Care Unit over 5 years within the frame of a routine therapeutic drug monitoring programme. Data were described using non-linear mixed-effects regression analysis ( nonmem®).
RESULTS: A total of 3039 gentamicin concentrations collected in 994 preterm and 455 term newborns were included in the analysis. A two compartment model best characterized gentamicin disposition. The average parameter estimates, for a median body weight of 2170 g, were clearance (CL) 0.089 l h(-1) (CV 28%), central volume of distribution (Vc ) 0.908 l (CV 18%), intercompartmental clearance (Q) 0.157 l h(-1) and peripheral volume of distribution (Vp ) 0.560 l. Body weight, gestational age and post-natal age positively influenced CL. Dopamine co-administration had a significant negative effect on CL, whereas the influence of indomethacin and furosemide was not significant. Both body weight and gestational age significantly influenced Vc . Model-based simulations confirmed that, compared with term neonates, preterm infants need higher doses, superior to 4 mg kg(-1) , at extended intervals to achieve adequate concentrations.
CONCLUSIONS: This observational study conducted in a large cohort of newborns confirms the importance of body weight and gestational age for dosage adjustment. The model will serve to set up dosing recommendations and elaborate a Bayesian tool for dosage individualization based on concentration monitoring.
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/06/2014 11:54
Dernière modification de la notice
20/08/2019 13:49
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