title: Effects of chronic levodopa therapy on dopa pharmacokinetics.
abstract: We reevaluate here the effects of chronic administration of levodopa on its peripheral pharmacokinetics and the contribution of the pharmacokinetics to the pathogenesis of the wearing-off phenomenon. The peak levodopa concentration (Cmax) and the area under the time-concentration curve (AUC) were markedly increased after long-term levodopa therapy, whereas the time to the peak concentration (Tmax) and the elimination half-life (T(1/2)) were decreased. These results suggest that long-term levodopa therapy accelerates the absorption of levodopa. Furthermore, the wearing-off group had a markedly higher Cmax and AUC, and a shorter Tmax and T(1/2) than the stable group. We speculate that the clinical expression of 'stable' or 'wearing-off' depends on the absorption of levodopa as well as the presynaptic terminal and postsynaptic receptors.
authors.affiliation: Department of Neurology, Institute for Brain Research, School of Medicine, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murata
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D004295:Dihydroxyphenylalanine / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008134:Long-Term Care; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009460:Neurologic Examination / Q000187:drug effects; D010300:Parkinson Disease / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D004295:Dihydroxyphenylalanine