Every 24-hour dosing of gentamicin in full-term neonates takes advantage of
these drug properties and is superior to multiple-daily dosing in terms of achievement of
higher peak concentrations and lower trough concentrations.
In neonates with HIE, gentamicin pharmacokinetics may be altered. Gentamicin is
eliminated almost exclusively by glomerular filtration4 and neonates with HIE often have
acute kidney dysfunction.In addition, hypothermia—an effective treatment modality for
HIE—may cause additional alterations in organ physiology and blood flow that impact
drug pharmacokinetics.But, in a recent clinical study of hypothermic versus
normothermic neonates with HIE, both groups had similar trough concentrations, suggesting
little effect of hypothermia on gentamicin pharmacokinetics. However, both groups
frequently had elevated trough concentrations >2 mg/L when receiving gentamicin 4-5 mg/
kg every 24 hours (44% of normothermic and 36% of hypothermic).This highlights the
need for a potential alternative dosing of gentamicin in the neonate with HIE. Given that
hypothermia is now recommended as the standard of care for moderate to severe HIE, an
understanding of gentamicin pharmacokinetics in the clinical context of hypothermia will be
necessary to help guide dose selection in this population. The objectives of this study were
1) to evaluate the pharmacokinetics of gentamicin in neonates with HIE receiving
hypothermia using a population-based approach and 2) to identify an empiric gentamicin
dosing strategy that optimizes achievement of target peak and trough drug concentrations.