title: Influence of mild hypothermia after hypoxia-ischemia on the pharmacokinetics of gentamicin in newborn pigs.
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.
authors.affiliation: Department of Pediatric, Ullevål University Hospital, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Satas
authors.forename: N O
authors.initials: NO
authors.lastname: Hoem
authors.forename: K
authors.initials: K
authors.lastname: Melby
authors.forename: H
authors.initials: H
authors.lastname: Porter
authors.forename: C G
authors.initials: CG
authors.lastname: Lindgren
authors.forename: A
authors.initials: A
authors.lastname: Whitelaw
authors.forename: M
authors.initials: M
authors.lastname: Thoresen
mesh_terms: 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
chemical_list: D001786:Blood Glucose; D005839:Gentamicins; D012964:Sodium; D003404:Creatinine; D011188:Potassium