Inhibition of canine and feline alcohol dehydrogenase activity by fomepizole.
OBJECTIVE
To determine and compare substrate specificity and kinetic rate constants of feline and canine alcohol dehydrogenase (ADH) with ethanol (EtOH) and ethylene glycol (EG) as substrates in vitro, with and without fomepizole.


METHODS
Livers from 3 dogs and 3 cats.


METHODS
Canine and feline ADH activity, in cytosolic fractions of homogenized liver, was determined by use of various concentrations of nicotinamide adenine dinucleotide (NAD), EtOH, or EG as substrates. Initial reaction velocities were calculated, and kinetic inhibition rate constants (Ki) for fomepizole were determined.


RESULTS
Substrate specificity of canine and feline ADH for EtOH or EG was not significantly different. A 2-fold difference was detected in the maximal velocity of canine, compared with feline, ADH, using either substrate. Fomepizole Ki in feline hepatic homogenates was significantly greater than Ki in canine hepatic homogenates when either EtOH or EG was used as substrate (10- and 30-fold, respectively). A 6-fold increase in the concentration of fomepizole was required to achieve ADH inhibition, with feline homogenates equivalent to those of canine homogenates.


CONCLUSIONS
Feline ADH has lower enzymatic capacity for turnover or is less concentrated in liver than canine ADH with regard to EtOH and EG catalysis. Canine ADH was more effectively inhibited by fomepizole than feline ADH. Results suggest that higher dosages of fomepizole may be more effective to treat cats with EG intoxication than dosages reported to treat dogs.
Connally
H E
HE
Department of Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523-1671, USA.
Hamar
D W
DW
Thrall
M A
MA
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002415:Cats / Q000378:metabolism*; D004285:Dogs / Q000378:metabolism*; D000077604:Fomepizole; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D011720:Pyrazoles / Q000494:pharmacology*; D013379:Substrate Specificity
D000931:Antidotes; D011720:Pyrazoles; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase