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 (T½) 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 T½ 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 receptor
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