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

The renal function is often affected in asphyxiated newborn infants. The ph armacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decre ase in body temperature is associated with a decrease in glomerular filtrat ion rate and may, therefore, impair the elimination of aminoglycosides. Whe n hypothermia is applied as neuronal rescue therapy after birth asphyxia, t he pharmacokinetics of kidney-eliminated drugs may be impaired even more. W e used our well-established global hypoxia-asphyxia newborn pig model to ev aluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed b y normothermia (39 degrees C) for 72 h (n = 8) or mild hypothermia (35 degr ees C) for 24 h followed by normothermia (39 degrees C) for 48 h (n = 8). G entamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normot hermia, and during normothermia 48 h after the first dose. The gentamicin p harmacokinetics variables were calculated using a SAAM II program. Hypoxia- ischemia altered renal function and gentamicin pharmacokinetics. The gentam icin clearance correlated with the creatinine plasma concentration (r = 0.8 9) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39 degrees C in newbor n pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables we re not different in the hypothermic or normothermic pigs after all three st udied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affe ct gentamicin pharmacokinetics. Copyright (C) 2000 S. Karger AG, Basel.