Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A routine gas chromatographic assay for urinary 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), the major metabolite of phenytoin (PHT) in man, was adapted to allow quantitation of 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin (Dihydrodiol, DHD) is based on the observation that acid-catalyzed dehydration of DHD quantitatively yields a mixture of p-HPPH and m-HPPH in a reproducible molar ratio of 56:44p-HPPH: m-HPPH and on the assumption that all m-HPPH found in urine after heating with acid has been derived from DHD. The urinary DHD content was verified by a "specific" method in which urine was incubated with beta-glucuronidase and the released phenolic metabolites completely removed by extraction. Subsequent acid-catalyzed dehydration of the remaining DHD yielded p-HPPH and m-HPPH, from the sum of which the original DHD concentration in urine could be calculated. In all of the urine samples from PHT patients examined to date, there was close agreement between the DHD values obtained by the "specific" method and those calculated from m-HPPH, in the simple acid-hydrolysis method. It can be inferred that much the greater part (greater than 90%) of m-HPPH found in human urine after acid treatment has been derived from DHD. All samples of urine after acid treatment has been derived from DHD. All samples of urine from PHT patients examined have shown detectable quantities of DHD. The methods described here may be useful in a survey of PHT patients to reveal unusual patterns of PHT metabolism and to permit recognition of possible associations between such unusual patterns and the occurrence of adverse reactions.
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PMID:Determination of 5-(3,4-Dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin (Dihydrodiol) and quantitative studies of phenytoin metabolism in man. 55 79

The effect of dose on the metabolism of phenytoin (5,5-diphenylhydantoin, DPH) was investigated. A single ip injection of 14C-DPH (1, 20, or 100 mg/kg) was given to adult male mice, and urine and feces were collected over 72 hr. DPH and its metabolites excreted in urine were separated and analyzed by HPLC after beta-glucuronidase hydrolysis and extraction with ethyl acetate. The drug-related products measured in urine included: DPH, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin, (DHD), 5-(3-methoxy-4-hydroxyphenyl)-5-phenylhydantoin (OMCAT), and diphenylhydantoic acid (DPHA). The percentage of the dose appearing as unchanged DPH and DPHA increased with dose, whereas that excreted as OMCAT decreased at higher doses. In contrast, the excretion of p-HPPH (approximately 30%) and DHD (approximately 12%) was independent of dose. The constant ratio of p-HPPH/DHD excreted in urine suggests that these metabolites have a common precursor, probably an arene oxide. Studies of the fate of DPH metabolites showed that a small fraction of a dose of p-HPPH or of DHD was converted to OMCAT. The catechol metabolite of DPH, therefore, arises via two different mechanisms.
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PMID:Phenytoin metabolism in mice. 612 2