Kinetics of fomepizole in pregnant rats.
OBJECTIVE
Fomepizole has been utilized with remarkable success for ethylene glycol and methanol poisonings in children and adults. However, very little information is available regarding the safe and effective use of fomepizole in pregnancy. The goal of this research was to utilize an animal model to investigate the kinetics of fomepizole in pregnancy.


METHODS
Male and pregnant Sprague-Dawley rats, which were obtained at 19 days gestation, were administered fomepizole 15 mg/kg intraperitoneally. The animals were anesthetized and blood, liver, kidney, and fetus samples were collected at 1-24 hours post administration. Tissue samples were homogenized, deproteinized and prepared by solid phase extraction. Fomepizole concentrations from tissue and serum samples were analyzed using high pressure liquid chromatography.


RESULTS
Between males and pregnant females, tissue and serum fomepizole levels were similar. Fomepizole concentrations in whole fetal tissue were similar to those in the maternal liver and kidney tissue. Fetal fomepizole concentrations were fivefold higher than maternal serum concentrations. The zero order elimination rate of fomepizole from maternal serum was 7.6 mol/L/h, which was slightly slower than the elimination rate in male rats (12.9 mol/L/h). Elimination of fomepizole from the fetus followed a similar time course to that in the maternal tissues.


CONCLUSIONS
Elevated concentrations of fomepizole were detected in the fetus following maternal administration. Although the levels of fomepizole in the fetal tissue would imply significant protection against fetal formation of toxic alcohol metabolites, further research is needed to explore the long-term effects of fomepizole on the fetus.
Department of Pharmacology, Toxicology and Neuroscience, Lousiana State University Health Sciences Center, Shreveport, LA 71130, USA.
Rebeca
R
Gracia
Brian
B
Latimer
Kenneth E
KE
McMartin
D000818:Animals; D000931:Antidotes / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005333:Fetus / Q000378:metabolism*; D000077604:Fomepizole; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011720:Pyrazoles / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013997:Time Factors; D014018:Tissue Distribution
D000931:Antidotes; D011720:Pyrazoles; D000077604:Fomepizole