Determination of 5-(P-Hydroxyphenyl)-5-Phenylhydantoin and Studies Relating to the Disposition of Phenytoin in Man

Witkin, Karen M.; Bius, Daniel L.; Teague, Betsy L.; Wiese, Lynn S.; Boyles, Larry W.; Dudley, Kenneth H.

doi:10.1097/00007691-197901000-00003

Cited by 9 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An acid-catalyzed release of metabolite conjugates from a urine sample was conducted using the procedure of Witkin et al (1979). Substitution of the IS (Fig.…”

Section: Urinary Mcat Glc Assaymentioning

confidence: 99%

See 1 more Smart Citation

Quantitative Estimation of Catechol/Methylcatechol Pathways in Human Phenytoin Metabolism

Maguire

1988

Epilepsia

View full text Add to dashboard Cite

A gas-liquid chromatographic (GLC) assay utilizing an on-column methylation technique has been developed to assay urinary concentration of a phenytoin (5,5-diphenylhydantoin, PHT) metabolite, 5-(4-hydroxy-3-methoxyphenyl)-5-phenylhydantoin (MCAT). Assay of MCAT in 35 24-h urine samples from patients receiving chronic phenytoin (PHT) therapy indicated that 0.3-4.0% of the daily dose could be accounted for as MCAT. The GLC assay was specific for MCAT, and provided a minimal estimate of the fraction of the PHT dose being metabolized via the catechol/MCAT route. Multiple regression analyses indicated that the amount of urinary MCAT was dependent on the quantities of both dihydrodiol (DHD) and p-phenolic (p-HPPH) metabolites. Oxidative pathways involving both DHD and p-HPPH as substrates appear to be responsible for catechol/MCAT production.

show abstract

“…An acid-catalyzed release of metabolite conjugates from a urine sample was conducted using the procedure of Witkin et al (1979). Substitution of the IS (Fig.…”

Section: Urinary Mcat Glc Assaymentioning

confidence: 99%

“…2A-C). The IS used in the method of Witkin et al (1979) did not allow sufficient resolution of MCAT to assay this ,metabolite. The only other modification of the reported procedure was the ad- ---dition of 500 mg Florid (100-200 mesh) to the final ethereal solution containing metabolites and IS.…”

Section: Urinary Mcat Glc Assaymentioning

confidence: 99%

Quantitative Estimation of Catechol/Methylcatechol Pathways in Human Phenytoin Metabolism

Maguire

1988

Epilepsia

View full text Add to dashboard Cite

show abstract

“…Samples of PHT, PHT-sodium, 5-(4-hydroxyphenyl)-5phenylhydantoin (p-HPPH), and 5-(4-methylphenyl)-5-phenylhydantoin (MPPH) were obtained from commercial sources (Parke Davis Co., Detroit, MI; Sigma Co., St. Louis, MO; Aldrich Chemical Co., Milwaukee, WI). Synthetic 5-(3-hydroxypheny1)-5-phenylhydantoin (m-HPPH) and 5-(4-hydroxyphenyl) -5-(4-methylphenyl)-hydantoin (HMPPH) were available from previous studies (Maguire et a]., 1978;Witkin et al, 1979), and trimethylphenylammonium hydroxide (TMPAH) solutions were prepared as previously described (Dudley et al, 1977). Enzymes were purchased from Sigma Chemical Co. : f3-glucuronidase (f3-Dglucuronide glucuronosohydrolase, EC 3.2.1.3 1) and arylsulfatase (aryl-sulfate sulfohydrolase, EC 3.1.6.1) from limpets.…”

Section: Reagentsmentioning

confidence: 99%

“…Gas-liquid chromatography PHT, p-HPPH, and dihydrodiol metabolite [DHD; 5-(3,4-dihydroxy-l,5-~yclohexadien-l-y1)-5phenylhydantoin] were derivatized with TMPAH and determined with an on-column methylation gasliquid chromatography (GLC) technique; the instrument and all gas flows were as reported (Maguire et al, 1979;Witkin et al, 1979). The column temperature was programmed from 190°C (O-min hold) to 250°C (8-min hold) at a rate of 16Wmin.…”

Section: Administration Of Drug and Collection Of Plasma Urine And mentioning

confidence: 99%

“…Acid-hydrolyzed feline urine was assayed by GLC essentially as previously described for human urine (Maguire et al, 1979;Witkin et al, 1979), with the modified column temperature program described above. To assay PHT, 10 kg/ml MPPH and 20 pg/ml HMPPH were included in the internal standard buffer solution (Witkin et al, 1979). Unconjugated PHT and metabolites in urine were assayed by the same method, except that the acidified sample was not heated.…”

Section: Urinementioning

confidence: 99%

See 1 more Smart Citation

Phenytoin Metabolism in the Cat After Long‐Term Oral Administration

et al. 1984

View full text Add to dashboard Cite

The metabolism of sodium phenytoin (PHT) in the cat was studied by gas-liquid chromatographic analyses of the drug and its metabolites extracted from plasma, urine, and feces during a 5-month course of daily oral administration. Plasma PHT levels of 15-18 micrograms/ml were observed. Urine contained 5-(4-hydroxyphenyl)-5-phenylhydantoin, 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)-5-phenylhydantoin, 1-deoxy-1-(5,5-diphenylhydantoin-3-yl)-beta-D-glucopyranuronate, and unmetabolized PHT. Large quantities of PHT (32-63% of the daily dose) were observed in feces. We suggest that gastrointestinal malabsorption, extensive N-glucuronidation, and limited hydroxylation determine the fate of orally administered PHT in the cat. This is not the case in humans.

show abstract

Phenytoin metabolism during pregnancy

Eadie

McKinnon

Dickinson

et al. 1992

Eur J Clin Pharmacol

View full text Add to dashboard Cite

The steady-state 72 h urinary excretion of various phenytoin metabolites has been measured in 10 epileptic women, whose plasma phenytoin concentrations relative to the phenytoin dose fell during pregnancy and rose again post-partum. In later pregnancy and post partum, a mean of 61.3% and 48.9%, respectively, of the total daily phenytoin dose was eliminated as 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). Even though p-HPPH accounts for not much more than half the total daily phenytoin dose, increased excretion of this metabolite sufficed to account for the elimination of the entire increase in the dose of phenytoin required during pregnancy. There was no definite increase in the excretion of any other (minor) metabolite measured. Thus pregnancy seems not to enhance uniformly the capacity of the various metabolic pathways of phenytoin.

show abstract

Determination of 5-(P-Hydroxyphenyl)-5-Phenylhydantoin and Studies Relating to the Disposition of Phenytoin in Man

Cited by 9 publications

References 0 publications

Quantitative Estimation of Catechol/Methylcatechol Pathways in Human Phenytoin Metabolism

Quantitative Estimation of Catechol/Methylcatechol Pathways in Human Phenytoin Metabolism

Phenytoin Metabolism in the Cat After Long‐Term Oral Administration

Phenytoin metabolism during pregnancy

Contact Info

Product

Resources

About