THE ON OFF PHENOMENON IN PARKINSONS-DISEASE - RELATION TO LEVODOPA ABSORPTION AND TRANSPORT
THE ON OFF PHENOMENON IN PARKINSONS-DISEASE - RELATION TO LEVODOPA ABSORPTION AND TRANSPORT
复制标题
DOI：
10.1056/nejm198402233100802
复制
发表时间：
1984-01-01
影响因子：
158.5
通讯作者：
ANDERSON, JL
中科院分区：
文献类型：
--
作者：
NUTT, JG;WOODWARD, WR;ANDERSON, JL
为了确定帕金森病患者对左旋多巴的振荡临床反应（开-关现象）是否反映了药物吸收和转运的波动，在具有振荡运动状态的患者中研究了这种现象。研究了对持续输注L-多巴的反应以及进餐对血浆L-多巴浓度和口服和静脉给药期间对临床反应的影响。膳食降低了29%的血浆左旋多巴浓度峰值和延迟吸收34分钟。通过持续输注药物的吸收产生了稳定的临床状态持续12小时，在所有的6例患者，并在一些长达36小时。高蛋白膳食或口服P、Leu或Ile（100 mg/kg体重）逆转了输注L-多巴的治疗效果，而不降低血浆L-多巴浓度。相同剂量的Gly和Lys没有影响。显然，食物对左旋多巴吸收的干扰以及大分子中性氨基酸与左旋多巴从血浆转运到大脑的竞争可能是帕金森病患者临床反应波动的部分原因。
To determine whether the oscillating clinical response to L-dopa in Parkinson''s disease (the on-off phenomenon) reflects fluctuations in absorption and transport of the drug, this phenomenon was studied in patients with an oscillating motor state. The response to continuous infusion of L-dopa and the effects of meals on the plasma L-dopa concentrations and on the clinical response during oral and i.v. administration of the drug was studied. Meals reduced peak plasma L-dopa concentrations by 29% and delayed absorption by 34 min. Bypassing absorption by constant infusion of the drug produced a stable clinical state lasting for 12 h in all of 6 patients and for up to 36 h in some. High protein meals or oral P, Leu or Ile (100 mg/kg of body wt) reversed the therapeutic effect of infused L-dopa without reducing plasma L-dopa concentrations. Gly and Lys at identical doses had no effect. Apparently, interference with absorption of L-dopa by food and by competition between large neutral amino acids and L-dopa for transport from plasma to the brain may be partly responsible for the fluctuating clinical response in patients with Parkinson''s disease.