Peak and Trough Concentrations of Gentamicin in the Neonate: A Review of the Literature

Gian   Maria   Pacifici

Abstract

Background: Sepsis is common in neonates and is a major cause of morbidity and mortality. 60% of preterm neonates receive at least one antibiotic and 43% of the antibiotics administered to these neonates are aminoglycosides. Gentamicin is an aminoglycoside which is largely used. Dosing of gentamicin gives rise to two concentrations, the peak concentration which is measured soon after dosing, and the trough concentration which is measured before the next administration. There has been a long debate about the appropriate dose of gentamicin to administer to neonates and the interval between doses. The ideal dosing of gentamicin should yield a peak concentration of 10μg/ml and a trough concentration of 1μg/ml. Objectives: The aim of this work is to compare the peak and trough concentrations of gentamicin in the neonate after twice-daily dosing, once-daily dosing and extended interval dosing to establish the safest one for neonates. Another aim of this note is to provide a critical analysis of the literature that can be a useful tool in the hands of physicians. Methods: The bibliographic search was performed electronically using PubMed, as the search engine, until January 14th 2008. Medline searches were performed with the following keywords “twice-daily dosing of gentamicin in neonates” with the limit of “human”; “once-daily dosing of gentamicin in neonates”; “extended interval dosing of gentamicin in neonates”; “pharmacokinetics of gentamicin in neonates”. In addition, the book Neofax: a Manual of Drugs Used in the Neonatal Care by Young and Mangum [2007] was consulted. Results: The peak and trough concentrations were compared after the following dosing schedules of gentamicin 2.5 mg/kg twice-daily dosing, 4 mg/kg once-daily dosing and 5 mg/kg every 48 h defined “extended interval dosing”. Twice-daily dosing was associated with the lowest peak gentamicin concentration and with the highest trough concentration. The lowest trough concentration was associated with the extended interval dosing of gentamicin. Gentamicin is mainly eliminated through glomerular filtration whose rate increases with the growth of the infant. The trough concentration was negatively correlated with the body weight indicating that in better developed neonates gentamicin was more rapidly eliminated. Conclusions: The dosing schedule contributes to determining the peak and trough concentrations of gentamicin in the neonate. There are numerous articles comparing the peak and trough concentrations after twice-daily dosing and oncedaily dosing of gentamicin. In contrast, little is known about the peak and trough concentration of extended interval dosing of gentamicin. More studies are required to better highlight the peak and trough concentrations of extended interval dosing of gentamicin at different gestational age.

Keywords: Gentamicin, peak-concentration, trough-concentration, pharmacokinetics, neonate

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