Pharmacokinetics of gentamicin in newborns with moderate-to-severe hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia.

Abstract

To investigate gentamicin pharmacokinetics in neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). Data were collected retrospectively from infants admitted between January 2007 and February 2011. Gentamicin was given at 2.5 mg/kg/dose q12h intravenously. Infants not eligible for TH underwent therapeutic normothermia (TN). After reviewing the data which showed >85 % of infants undergoing TH had gentamicin trough concentration >2 µg/ml at steady state, the gentamicin level monitoring protocol was modified since March 2011. In the initial retrospective study, 15 TN infants were compared with 19 TH infants. There was significant difference in median gentamicin half-life (7.01 vs. 9.57 h). A higher proportion of infants in the TH group required dosage adjustment (8/15 vs. 17/19). After March 2011, gentamicin level taken 12-h post 1st dose was measured routinely and 18/22 infants had trough gentamicin levels >2 µg/ml. Their dosing intervals were extended to Q18h or beyond. Infants with moderate-to-severe HIE who undergo TH may exhibit changes in the pharmacokinetic properties of gentamicin compared to infants who undergo TN. By measuring gentamicin level at 12-h after the first dose of 2.5 mg/kg/dose, appropriate dosing interval can be determined and the duration of exposure to toxic gentamicin level can be reduced.