Disease relevance of p-Hydroxyphenytoin

• The mutagenicities of 5,5-diphenylhydantoin (DPH) and its major metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) were tested in vitro using different Salmonella strains (TA1535, TA100, TA1537, TA1538, TA98) [1].
• Phenytoin and its metabolite, 5-(4-hydroxyphenyl)-5-phenylhydantoin, show bone resorption in cultured neonatal mouse calvaria [2].
• The potential effect of co-medication with phenobarbitone, primidone and carbamazepine on plasma and saliva concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin (4-HPPH), the major metabolite of phenytoin in man and on the incidence of phenytoin-induced gingival overgrowth was investigated in a group of 36 adult epileptic patients [3].

High impact information on p-Hydroxyphenytoin

• Plasma samples for phenytoin and cimetidine, and urinary concentrations for phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) were measured by HPLC [4].
• Moreover, the amino acid substitution decreased the enantiomeric excess in the formation of 5-(4-hydroxyphenyl)-5-phenylhydantoin from phenytoin [5].
• Analysis of mephenytoin, 4-hydroxymephenytoin and 4-hydroxyphenytoin enantiomers in human urine by cyclodextrin micellar electrokinetic capillary chromatography: simple determination of a hydroxylation polymorphism in man [6].
• The cytochrome P450-dependent covalent binding of radiolabel derived from phenytoin (DPH) and its phenol and catechol metabolites, 5-(4'-hydroxyphenyl)-5-phenylhydantoin (HPPH) and 5-(3',4'-dihydroxyphenyl)-5-phenylhydantoin (CAT), was examined in liver microsomes [7].
• Phenytoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin do not alter the effects of bacterial and amplified plaque extracts on cultures of fibroblasts from normal and overgrown gingivae [8].

Biological context of p-Hydroxyphenytoin

• The elimination kinetics of p- hydroxyphenytoin , the major metabolite of phenytoin which inhibits phenytoin metabolism in rats, were similar in pregnant and nonpregnant rats and so were the plasma concentrations of this metabolite after phenytoin administration [9].
• Incubation of possible precursor metabolites to the catechol indicate that the sex difference in catechol formation is due to differences in 5-(4-hydroxyphenyl)-5-phenylhydantoin hydroxylation rather than to differences in oxidation of the dihydrodiol metabolite [10].
• Following acid hydrolysis of the hydroxyphenytoin glucuronic acid conjugate the sample is diluted with water and after centrifugation is injected onto the pre-column [11].
• The mutagenicity of diphenylhydantoin (DPH) and its major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), has been re-evaluated by the Ames test using Salmonella typhimurium and, for DPH only, by an in vitro cytogenetic test with human lymphocytes and a turbidimetric assay of tubulin polymerization [12].
• A reinvestigation of the alkylation of 5-(p-hydroxyphenyl)-5-phenylhydantoin [13].

Anatomical context of p-Hydroxyphenytoin

• Fibroblasts from healthy and overgrown gingivae were incubated with (a) PHT and its major human metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), (b) microbial and "amplified" plaque extracts, and (c) microbial and "amplified" plaque extracts plus PHT and HPPH [8].
• The nature of the inhibitory effects of the major metabolite of diphenylhydantoin, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), on the in vitro metabolism of ethylmorphine and aniline by rat hepatic microsomes was examined [14].
• After simple purification of the incubation mixture of phenytoin in isolated rat hepatocytes, 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH), which formed as a major metabolite, was readily resolved to each enantiomer by direct high-performance liquid chromatography on a cellulose tris(4-methylbenzoate) column, with a mobile phase of ethanol-water [15].
• Gas chromatography/mass spectrometry was employed for analyses of phenytoin and three metabolites - 5-(4-hydroxyphenyl)-5-phenylhydantoin, methylated 3,4-catechol, and 3,4-dihydrodiol - in blood, urine, and feces [16].

Associations of p-Hydroxyphenytoin with other chemical compounds

• Crossover studies were conducted to compare plasma levels of phenytoin and urinary throughput of the major metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin (HPPH), after ingestion of single 250-mg oral doses as tablets or as capsules [17].
• Biointeraction studies based on high performance affinity chromatography were used to investigate the binding of human serum albumin (HSA) to two major phenytoin metabolites: 5-(3-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) [18].

Gene context of p-Hydroxyphenytoin

• Among them, phenytoin has been used as a probe to determine CYP2C9 phenotype by measuring the urinary excretion of its major metabolite, S-enantiomer of 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) [19].
• The urinary excretion profiles of the metabolites of PHT, (R)- and (S)-p-HPPH [5-(4-hydroxyphenyl)-5-phenylhydantoin] up to 361 postdose were compared between the two groups of poor metabolizers (PMs, n = 3) and extensive metabolizers (EMs, n = 3) with respect to CYP2C19 [20].

Analytical, diagnostic and therapeutic context of p-Hydroxyphenytoin

• Plasma phenytoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and urine S and R enantiomers of p-HPPH were determined by high-performance liquid chromatography [21].
• Thin-layer chromatography showed only PHT in the brain 15 min after injection of PHT and both PHT and its hydroxylated metabolite [5-(p-hydroxyphenyl)-5-phenylhydantoin] 120 min after injection [22].
• 5,5-Diphenylhydantoin or 5-(4-hydroxyphenyl)-5-phenylhydantoin, 3.6 X 10(-4) M, inhibited polymerization of purified pig brain tubulin 50% as measured by viscosometric assay and estimation of tubulin length by electron microscopy [23].
• The analysis was performed for the m- and p-isomers of hydroxyphenytoin, the oxidative products of phenytoin, using gas chromatography [24].
• All samples were assayed for phenytoin and p-hydroxydiphenylhydantoin by liquid scintillation counting following separation by TLC [25].

References