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.