Population pharmacokinetic study of gentamicin in a large cohort of premature and term neonates.
Br J Clin Pharmacol
; 78(5): 1090-101, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-24938850
ABSTRACT
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recém-Nascido
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Recém-Nascido Prematuro
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Gentamicinas
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Antibacterianos
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Modelos Biológicos
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Guideline
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article