Acute moderate hypoxia reduces ethanol elimination in the conscious rabbit.
Hypoxic states decrease the catalytic activity of certain enzymes of the cytochrome P450, leading to decreased clearance of selected xenobiotics. It is not known whether hypoxia can affect the activity of cytosolic enzymes such as liver alcohol dehydrogenase (LADH). This study was carried out to examine the effect of experimentally induced acute moderate hypoxia on the kinetics of ethanol and on the catalytic activity of LADH in the conscious rabbit. To this purpose, the kinetics of elimination of ethanol (70 mg/kg intravenously) were studied in male rabbits (n = 6) kept in an atmosphere with a fractional concentration of O2 (FiO2) of 0.12 for 24 h, and in rabbits (n = 6) breathing room air with a FiO2 approximately 0.21 (controls). Compared with controls, the clearance of ethanol was reduced by 32% (P < 0.05) in rabbits exposed to acute moderate hypoxia. In rabbits that consumed approximately 6 g/kg/day ethanol in their drinking water for 14 days (n = 6), acute moderate hypoxia reduced the clearance of ethanol to the same extent as observed in rabbits receiving a single dose of ethanol. Hypoxia did not change the in vitro Vmax or Km of LADH. This study demonstrates that acute moderate hypoxia reduces the clearance of ethanol following single or multiple administrations.
Gavalakis
J
J
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Quebec, Canada.
du Souich
P
P
Sharkawi
M
M
D000208:Acute Disease; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D019540:Area Under Curve; D002492:Central Nervous System Depressants / Q000097:blood / Q000493:pharmacokinetics*; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D000860:Hypoxia / Q000378:metabolism*; D007275:Injections, Intravenous; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011817:Rabbits
D002492:Central Nervous System Depressants; D000431:Ethanol; D000426:Alcohol Dehydrogenase