Entrapment of bioactive compounds within native albumin beads: II. Effects of rate and extent of crosslinking on microbead properties.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M A Moustafa
Publications and source records attributed to M A Moustafa.
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.
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.
Adult↗
Evidence for an arene-3,4-oxide as a metabolic intermediate in the meta- and para-hydroxylation of phenytoin in the dog.
To investigate the potential involvement of an arene oxide-NIH shift pathway in the meta- and para-hydroxylation of phenytoin, (R,S)-5-(2-deuteriophenyl)-5-phenylhydantoin (2-2H-DPH), (R,S)-5-(3-deuteriophenyl)-5-phenylhydantoin (3-2H-DPH), and (R,S)-5-(4-deuteriophenyl)-5-phenylhydantoin (4-2H-DPH) were subjected to in vivo metabolic experiments in the dog. After enzymatic hydrolysis of the urine, meta- and para-hydroxy metabolites were isolated by HPLC and deuterium retentions were determined by GC/MS. The metahydroxy metabolites had 100, 52, and 80-82% retained of their initial deuterium content after oral administration of (R,S)-2-, 3-, and 4-2H-DPH, respectively. Similarly, in the case of the para-hydroxy metabolites, the percentages of deuterium retained were 100, 92, and 71-72%. These results exclude the intermediacy of a DPH-2,3-oxide in the production of meta-hydroxy metabolites but are consistent with the existence of DPH-3,4-oxide as intermediate in the production of both meta- and para-hydroxy metabolites. The stereoselectivity of the meta- and para-hydroxylation has been determined by GC/MS analyses of the urinary metabolites after administration of (R)-5-(3-deuteriophenyl)-5-phenylhydantoin [(R)-3-2H-DPH], and the measurements are in agreement with previous determinations in the literature obtained by optical methods. The overall results of 2H retention are compared with those obtained in the rabbit, rat, and man.
Animals↗