PHENYTOIN PARAHYDROXYLATION IS NOT IMPAIRED IN PATIENTS WITH YOUNG-ONSET PARKINSONS-DISEASE

Impaired hepatic detoxification capacity by cytochrome P450 subsystems has been implicated in the pathogenesis of Parkinson's disease. We ha ve demonstrated that hepatic parahydroxylation of phenytoin (PHT) is i mpaired in patients with late-onset Parkinson's disease. In the presen t study, we have investigated the hypothesis that PHT parahydroxylatio n is even more impaired in patients with young-onset Parkinson's disea se (age at onset before 40 years). We determined PHT parahydroxylation capacity in 21 patients with young-onset Parkinson's disease and 15 h ealthy age-matched controls. PHT parahydroxylation capacity was assess ed by measuring the ratio of PHT to its major metabolite p-hydroxyphen yl-phenylhydantoin in serum 6 h after an oral test dose of 300 mg PHT. PHT parahydroxylation did not differ significantly between patients a nd controls. These results argue against the hypothesis that impaired activity of the cytochrome P450 isoenzyme responsible for PHT parahydr oxylation is involved in the etiology of Parkinson's disease.