Effects of hypothermia on the elimination of ethanol, diazepam and oxazepam in rat liver slice incubations.
The elimination of ethanol, diazepam and oxazepam which are metabolised by different enzymes, has been studied for 30, 60, 90 and 120 min at 37, 27, 17 and 7 degrees C in rat liver slice incubations. Ethanol elimination followed zero-order kinetics at all temperatures, while the benzodiazepines consistently displayed first-order kinetics. No sign of phase transition was observed in the respective Arrhenius-plots. Ethanol elimination was more temperature dependent than the elimination of diazepam, while the elimination of oxazepam was little influenced by temperature. This is shown by the temperature ratios (Q10) and energies of activation (Ea) of 1.76, 1.56, 1.24 and 40.5, 31.9, 15.2 for ethanol, diazepam and oxazepam, respectively. This means that ethanol, diazepam and oxazepam elimination was reduced by 25, 22 and 14%, respectively, for each 10 degrees C of temperature reduction, which is considerably lower than the commonly observed 50% reduction of enzyme activity. We conclude that observations made for one drug on temperature dependent elimination may not apply to other drugs.
Mortensen
B
B
University of Trondheim, Department of Pharmacology and Toxicology, Norway.
Dale
O
O
D000818:Animals; D001831:Body Temperature; D003080:Cold Temperature; D003975:Diazepam / Q000032:analysis / Q000493:pharmacokinetics*; D000431:Ethanol / Q000032:analysis / Q000493:pharmacokinetics*; D016014:Linear Models; D008099:Liver / Q000378:metabolism*; D008297:Male; D010076:Oxazepam / Q000032:analysis / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000431:Ethanol; D010076:Oxazepam; D003975:Diazepam