Journal article
Metabolism of 2-chloro-1,1-difluoroethene to glyoxylic and glycolic acid in rat hepatic microsomes
Drug metabolism and disposition, Vol.18(5), pp.753-758
09/1990
DOI: 10.1016/S0090-9556(25)08647-7
PMID: 1981732
Abstract
The complete metabolic fate of the volatile anesthetic halothane is unclear since 2-chloro-1,1-diflurorethene (CDE), a reductive halothane metabolite, is known to readily release inorganic fluoride upon oxidation by cytochrome P-450. This study sought to clarify the metabolism of CDE by determining its metabolites and the roles of induce cytochrome P-450 forms in its metabolism. Upon incubation of [14C]CDE with rat hepatic microsomes, two major radioactive products were found which accounted for greater than 94% of the total metabolites. These compounds were determined to be the nonhalogenated compounds, glyoxylic and glycolic acids, which were formed in a ratio of approximately 1 to 2 of glyoxylic to glycolic acid. No other radioactive metabolites could be detected. Following incubation of CDE with hepatic microsomes isolated from rats treated with cytochrome P-450 inducers, measurement of fluoride release showed that phenobarbital induced CDE metabolism to the greatest degree at high CDE levels, isoniazid was the most effective inducer at low CDE concentrations, and beta-naphthoflavone was ineffective as an inducer. These results suggest that CDE biotransformation primarily involves the generation of an epoxide intermediate, which undergoes mechanisms of decay leading to total dehalogenation of the molecule, and that this metabolism is preferentially carried out by the phenobarbital- and ethanol-inducible forms of cytochrome P-450.
Details
- Title: Subtitle
- Metabolism of 2-chloro-1,1-difluoroethene to glyoxylic and glycolic acid in rat hepatic microsomes
- Creators
- Max T Baker - Department of Anesthesia, University of IowaMaria T VasquezJames N BatesChao-Kuo Chiang
- Resource Type
- Journal article
- Publication Details
- Drug metabolism and disposition, Vol.18(5), pp.753-758
- Publisher
- United States
- DOI
- 10.1016/S0090-9556(25)08647-7
- PMID
- 1981732
- ISSN
- 0090-9556
- eISSN
- 1521-009X
- Language
- English
- Date published
- 09/1990
- Academic Unit
- Anesthesia
- Record Identifier
- 9984006452502771
Metrics
14 Record Views