Influence of mild hypothermia after hypoxia-ischemia on the pharmacokinetics of gentamicin in newborn pigs

Biol Neonate. 2000;77(1):50-7. doi: 10.1159/000014195.

Abstract

The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39 degrees C) for 72 h (n = 8) or mild hypothermia (35 degrees C) for 24 h followed by normothermia (39 degrees C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39 degrees C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blood Glucose / analysis
  • Creatinine / blood
  • Female
  • Fluorescence Polarization Immunoassay
  • Gentamicins / administration & dosage
  • Gentamicins / blood
  • Gentamicins / pharmacokinetics*
  • Half-Life
  • Hypothermia, Induced
  • Hypoxia / metabolism*
  • Ischemia / metabolism*
  • Kidney / pathology
  • Male
  • Models, Biological
  • Potassium / blood
  • Random Allocation
  • Rewarming
  • Sodium / blood
  • Swine

Substances

  • Blood Glucose
  • Gentamicins
  • Sodium
  • Creatinine
  • Potassium