Chronic levodopa therapy enhances dopa absorption: contribution to wearing-off.
Effects of the chronic administration of levodopa on its peripheral pharmacokinetics and the contribution of the pharmacokinetics to the pathogenesis of the wearing-off phenomenon are re-evaluated. The concentration of plasma levodopa and clinical symptoms were determined 4 hours after oral levodopa (levodopa 100 mg + benserazide 25 mg) administration on 55 parkinsonian patients. Long-term levodopa therapy markedly increased the peak levodopa concentration (Cmax) and the area under the time-concentration curve (AUC); whereas, it decreased time to the peak concentration (Tmax) and the elimination half-life (T1/2). These results suggest that long-term levodopa therapy accelerates the absorption of levodopa. The wearing-off group (n = 23), however, had a markedly higher Cmax and AUC, and a shorter Tmax and T1/2 than the stable group (n = 32). We speculate that the clinical expression of "stable" or "wearing-off" depends on the absorption of levodopa as well as the presynaptic terminal and post synaptic receptors.
Murata
M
M
Department of Neurology, University of Tokyo, Japan.
Mizusawa
H
H
Yamanouchi
H
H
Kanazawa
I
I
D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D004386:Duodenum / Q000201:enzymology; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism
D000978:Antiparkinson Agents; D007980:Levodopa; D001142:Aromatic-L-Amino-Acid Decarboxylases