Murata M, Mizusawa H, Yamanouchi H, Kanazawa I
Department of Neurology, University of Tokyo, Japan.
J Neural Transm (Vienna). 1996;103(10):1177-85. doi: 10.1007/BF01271202.
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.
重新评估了长期服用左旋多巴对其外周药代动力学的影响以及药代动力学对剂末现象发病机制的作用。在55例帕金森病患者口服左旋多巴（左旋多巴100mg + 苄丝肼25mg）4小时后，测定血浆左旋多巴浓度和临床症状。长期左旋多巴治疗显著提高了左旋多巴的峰值浓度（Cmax）和时间 - 浓度曲线下面积（AUC）；然而，它缩短了达到峰值浓度的时间（Tmax）和消除半衰期（T1/2）。这些结果表明，长期左旋多巴治疗加速了左旋多巴的吸收。然而，剂末现象组（n = 23）的Cmax和AUC明显高于稳定组（n = 32），Tmax和T1/2则更短。我们推测，“稳定”或“剂末现象”的临床表现取决于左旋多巴的吸收以及突触前末端和突触后受体。
