Kinetics of fomepizole in pregnant rats. 2012

Rebeca Gracia, and Brian Latimer, and Kenneth E McMartin
Department of Pharmacology, Toxicology and Neuroscience, Lousiana State University Health Sciences Center, Shreveport, LA 71130, USA.

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.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007668 Kidney Body organ that filters blood for the secretion of URINE and that regulates ion concentrations. Kidneys
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008297 Male Males
D011247 Pregnancy The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH. Gestation,Pregnancies
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D005260 Female Females
D005333 Fetus The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN. Fetal Structures,Fetal Tissue,Fetuses,Mummified Fetus,Retained Fetus,Fetal Structure,Fetal Tissues,Fetus, Mummified,Fetus, Retained,Structure, Fetal,Structures, Fetal,Tissue, Fetal,Tissues, Fetal
D000077604 Fomepizole A pyrazole and competitive inhibitor of ALCOHOL DEHYDROGENASE that is used for the treatment of poisoning by ETHYLENE GLYCOL or METHANOL. 4-Methylpyrazole,4-Methylpyrazole Monohydrochloride,Antizol,4 Methylpyrazole,4 Methylpyrazole Monohydrochloride

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