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 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.
Satas
S
S
Department of Pediatric, Ullevål University Hospital, Oslo, Norway.
Hoem
N O
NO
Melby
K
K
Porter
H
H
Lindgren
C G
CG
Whitelaw
A
A
Thoresen
M
M
D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000032:analysis; D003404:Creatinine / Q000097:blood; D005260:Female; D016231:Fluorescence Polarization Immunoassay; D005839:Gentamicins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D007036:Hypothermia, Induced; D000860:Hypoxia / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D008297:Male; D008954:Models, Biological; D011188:Potassium / Q000097:blood; D011897:Random Allocation; D017694:Rewarming; D012964:Sodium / Q000097:blood; D013552:Swine
D001786:Blood Glucose; D005839:Gentamicins; D012964:Sodium; D003404:Creatinine; D011188:Potassium