Evidence for an arene oxide-NIH shift pathway in the metabolic conversion of phenytoin to 5-(4-hydroxyphenyl)-5-phenylhydantoin in the rat and in man
Journal Article
·
· Drug Metab. Dispos.; (United States)
OSTI ID:6217150
To determine whether the hydroxylation of 5,5-diphenylhydantoin (DPH) to 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) occurs by an arene oxide-NIH shift process, racemic 5-(4-deuteriophenyl)-5-phenylhydantoin (p-2H-DPH) was subjected to in vivo metabolic experiments in the rat and in man. After enzymatic hydrolysis of the urine, para-hydroxylated metabolites were separated by HPLC. Deuterium retention in the isolated metabolites determined by gas chromatography-mass spectrometry, was 68-72%. The results are interpreted as the predominance of an arene oxide-NIH shift pathway in those two metabolic systems. Induction of rats with phenobarbital or 3-methylcholanthrene showed no effect on the value of deuterium retention.
- Research Organization:
- Department of Medicinal Chemistry, School of Pharmacy, University of Louvain
- OSTI ID:
- 6217150
- Journal Information:
- Drug Metab. Dispos.; (United States), Journal Name: Drug Metab. Dispos.; (United States) Vol. 10:6; ISSN DMDSA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
560306* -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTICONVULSANTS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOLOGICAL WASTES
BODY FLUIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL ANALYSIS
DISEASES
DRUGS
EPILEPSY
IN VIVO
MAMMALS
MATERIALS
METABOLISM
NERVOUS SYSTEM DISEASES
PATIENTS
QUALITATIVE CHEMICAL ANALYSIS
RATS
RODENTS
URINE
VERTEBRATES
WASTES
560306* -- Chemicals Metabolism & Toxicology-- Man-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTICONVULSANTS
BIOLOGICAL MATERIALS
BIOLOGICAL PATHWAYS
BIOLOGICAL WASTES
BODY FLUIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL ANALYSIS
DISEASES
DRUGS
EPILEPSY
IN VIVO
MAMMALS
MATERIALS
METABOLISM
NERVOUS SYSTEM DISEASES
PATIENTS
QUALITATIVE CHEMICAL ANALYSIS
RATS
RODENTS
URINE
VERTEBRATES
WASTES