Joseph Y Ting1, Eddie Kwan, Al McDougal, Horacio Osiovich. 1. Division of Neonatology, Department of Pediatrics, University of British Columbia, 1R46A - 4480 Oak Street, Vancouver, V6H 3V4, BC, Canada, jting2@cw.bc.ca.
Abstract
OBJECTIVE: To investigate gentamicin pharmacokinetics in neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: To investigate gentamicin pharmacokinetics in neonates with moderate-to-severe hypoxic-ischemicencephalopathy (HIE) who underwent therapeutic hypothermia (TH). METHODS: 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. RESULTS: 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. CONCLUSIONS: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.
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