Effects of chronic levodopa therapy on dopa pharmacokinetics.
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.
Murata
M
M
Department of Neurology, Institute for Brain Research, School of Medicine, University of Tokyo, Japan.
Kanazawa
I
I
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
D000978:Antiparkinson Agents; D007980:Levodopa; D004295:Dihydroxyphenylalanine