帕金森病左旋多巴效应室浓度效应关系的研究

The comparative study on effect site concentration effect relationship of levodopa in Parkinsons disease.

目的 根据左旋多巴（ＬＤ） 效应室浓度效应关系的差异探讨帕金森病（ＰＤ） 症状波动的发生原因和防治对策。方法 测定症状稳定（ＳＰ） 和症状波动（ＦＰ）ＰＤ 病人服单剂量ＬＤ 后的多时点血药浓度，同时动态观察相应的临床症状改善程度，根据Ｓｈｅｉｎｅｒ 效应室模型理论推导出两组病人的ＬＤ 效应室浓度药物效应的关系曲线，比较两者曲线参数的差异。结果 ＳＰ 和ＦＰ的ＬＤ 效应室浓度药物效应关系曲线的参数有较大的差异，ＥＣ５０ 、Ｈｉｌｌ 系数与病程、病级、ＬＤ 疗程正相关，Ｔ１／２ｅｑ与病程、病级、ＬＤ 疗程负相关。结论 ＬＤ 效应室药物浓度效应关系是研究ＰＤ 长期治疗后临床效应变化的有效方法。ＰＤ临床药效学变化规律对ＰＤ 症状波动的治疗有指导意义。

Objective To explore the mechanism of fluctuation in Parkinsonian patients and corresponding prophylactic and therapeutical strategies by comparing the effect site concentration effect relationship of levodopa in fluctuating and stable patients with Parkinsons diseased(PD).Methods The plasma levodopa concentration and corresponding motor response in 15 stable and 15 fluctuating patients with PD were detected after a single dose of levodopa. The parameters (EC50\, Ke0\, HILL COEFFICIENT\, T1/2eq) of the effect site concentration effect relationship were conducted by Sheiners theory and compared between stable and fluctuating patients. Results The parameters of the effect site concentration effect relationship between stable and fluctuating patients were quite different.EC50 and Hill coefficient had positwe relations with the causes, the levodopa therapeutical time as well as the severity of PD, but T 1/2eq had negative relations with the above fators. Conclusions Sheiners theory make a practical way for clinical doctors to gain the effect site concentration relationship with an uninvasive mthod. The prophylactic and therapeutical methods according to the effect site concentration effect relationship changes are usefulto to guide the treatment of PD.