title: Phenytoin parahydroxylation is not impaired in patients with young-onset Parkinson's disease.
abstract: Impaired hepatic detoxification capacity by cytochrome P450 subsystems has been implicated in the pathogenesis of Parkinson's disease. We have demonstrated that hepatic parahydroxylation of phenytoin (PHT) is impaired in patients with late-onset Parkinson's disease. In the present study, we have investigated the hypothesis that PHT parahydroxylation is even more impaired in patients with young-onset Parkinson's disease (age at onset before 40 years). We determined PHT parahydroxylation capacity in 21 patients with young-onset Parkinson's disease and 15 healthy age-matched controls. PHT parahydroxylation capacity was assessed by measuring the ratio of PHT to its major metabolite p-hydroxyphenyl-phenylhydantoin in serum 6 h after an oral test dose of 300 mg PHT. PHT parahydroxylation did not differ significantly between patients and controls. These results argue against the hypothesis that impaired activity of the cytochrome P450 isoenzyme responsible for PHT parahydroxylation is involved in the etiology of Parkinson's disease.
authors.affiliation: Department of Neurology, University Hospital Leiden, The Netherlands.
authors.forename: E A
authors.initials: EA
authors.lastname: Peeters
authors.forename: B R
authors.initials: BR
authors.lastname: Bloem
authors.forename: M A
authors.initials: MA
authors.lastname: Kuiper
authors.forename: P
authors.initials: P
authors.lastname: Vermeij
authors.forename: F A
authors.initials: FA
authors.lastname: de Wolff
authors.forename: E C
authors.initials: EC
authors.lastname: Wolters
authors.forename: R A
authors.initials: RA
authors.lastname: Roos
authors.forename: M D
authors.initials: MD
authors.lastname: Ferrari
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D007527:Isoenzymes / Q000502:physiology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D010300:Parkinson Disease / Q000201:enzymology*; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D012016:Reference Values
chemical_list: D007527:Isoenzymes; C027364:5-(3-hydroxyphenyl)-5-phenylhydantoin; D010672:Phenytoin; D003577:Cytochrome P-450 Enzyme System