Journal
THERAPEUTIC DRUG MONITORING
Volume 35, Issue 2, Pages 217-222Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FTD.0b013e3182834335
Keywords
hypoxic ischemic encephalopathy; cooling; aminoglycoside
Funding
- Pediatric Pharmacy Advocacy Group and Neonatal Pharmacy Research Grant
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Objective: To identify whether therapeutic hypothermia in new-borns with hypoxic ischemic encephalopathy affects gentamicin pharmacokinetics. Study Design: Retrospective case-control study consisting of 16 neonates who underwent therapeutic hypothermia and received gentamicin with interpretable peak and trough serum levels obtained during the period of cooling and at steady state; comparator group consisting of 7 neonates met the criteria but did not undergo therapeutic hypothermia. Results: Significant differences in gentamicin pharmacokinetics were noted between the therapeutic hypothermia group and the comparator group in elimination rate constant (0.08/h versus 0.11/h; P < 0.01), elimination half-life (9.16 hours versus 6.56 hours; P < 0.01), and clearance (0.04 L/kg.h(-1) versus 0.05 L/kg.h(-1); P < 0.01), respectively. Higher gentamicin trough serum concentrations were seen with the therapeutic hypothermia group (1.68 mcg/mL versus 0.77 mcg/mL; P < 0.01). Conclusions: Therapeutic hypothermia is associated with alterations in gentamicin pharmacokinetics, reducing gentamicin clearance by 25.5% in neonates with hypoxic ischemic encephalopathy, which may result in increased trough serum concentrations.
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