Quantitative estimation of catechol/methylcatechol pathways in human phenytoin metabolism.
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.
Maguire
J H
JH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599-7360.
D002396:Catechols / Q000378:metabolism / Q000652:urine*; D004827:Epilepsy / Q000188:drug therapy / Q000652:urine; D006801:Humans; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000627:therapeutic use / Q000652:urine
D002396:Catechols; C001419:hydroxyphenytoin; C038540:5-(3,4-dihydroxyphenyl)-5-phenylhydantoin; C057787:5-(4-hydroxy-3-methoxyphenyl)-5-phenylhydantoin; D010672:Phenytoin