Document Detail


Kinetics of fomepizole in pregnant rats.
MedLine Citation:
PMID:  22891985     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT/OBJECTIVES: 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.
MATERIALS/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.
DISCUSSION/CONCLUSION: 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.
Authors:
Rebeca Gracia; Brian Latimer; Kenneth E McMartin
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Publication Detail:
Type:  Journal Article     Date:  2012-08-14
Journal Detail:
Title:  Clinical toxicology (Philadelphia, Pa.)     Volume:  50     ISSN:  1556-9519     ISO Abbreviation:  Clin Toxicol (Phila)     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-28     Completed Date:  2012-11-05     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101241654     Medline TA:  Clin Toxicol (Phila)     Country:  England    
Other Details:
Languages:  eng     Pagination:  743-8     Citation Subset:  AIM; IM    
Affiliation:
Department of Pharmacology, Toxicology and Neuroscience, Lousiana State University Health Sciences Center, Shreveport, LA 71130, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antidotes / pharmacokinetics*
Chromatography, High Pressure Liquid
Female
Fetus / metabolism*
Injections, Intraperitoneal
Kidney / metabolism
Liver / metabolism
Male
Pregnancy
Pyrazoles / pharmacokinetics*
Rats
Rats, Sprague-Dawley
Sex Factors
Time Factors
Tissue Distribution
Chemical
Reg. No./Substance:
0/Antidotes; 0/Pyrazoles; 83LCM6L2BY/fomepizole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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