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

Indian J Pediatr. 2015 Feb;82(2):119-25. doi: 10.1007/s12098-014-1527-z. Epub 2014 Jul 29.

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.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Drug Monitoring
  • Drug-Related Side Effects and Adverse Reactions* / etiology
  • Drug-Related Side Effects and Adverse Reactions* / prevention & control
  • Female
  • Gentamicins* / administration & dosage
  • Gentamicins* / adverse effects
  • Gentamicins* / pharmacokinetics
  • Humans
  • Hypothermia, Induced / methods*
  • Hypoxia-Ischemia, Brain* / diagnosis
  • Hypoxia-Ischemia, Brain* / physiopathology
  • Hypoxia-Ischemia, Brain* / therapy
  • Infant, Newborn
  • Male
  • Retrospective Studies
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Gentamicins