Quinn N, Marsden C D, Parkes J D
Lancet. 1982 Aug 21;2(8295):412-5. doi: 10.1016/s0140-6736(82)90442-1.
The cause(s) of response fluctuations in patients with Parkinson's disease treated chronically with levodopa is unknown. In some subjects it is difficult to establish a clear relation between levodopa dosage and timing and the resultant clinical effects. This may be due to variation in the degree of absorption of the drug, and in the latency from ingestion to peak plasma level and from plasma peak to central action. In one patient illustrated, careful analysis of "on-off" charts reveals an underlying pattern of end-of-dose deterioration at a time when history alone suggested a completely random response to levodopa. In three patients replacement of oral treatment by continuous intravenous infusion of levodopa, with oral administration of decarboxylase inhibitor, produced a prolonged and stable clinical response, even when ambulant. This response was maintained not only in one subject showing predictable fluctuations, but also in two subjects with unpredictable response to oral treatment. The addition of intravenous levodopa infusion to the usual oral regimen of the first patient when she was experiencing prolonged "off" periods despite generous doses of oral levodopa with decarboxylase inhibitor also produced stable clinical benefit. These results suggest that, even in patients with complicated response swings, central dopamine receptors remain available for stimulation providing levodopa can be delivered at a constant rate and in an adequate quantity to the brain.
长期接受左旋多巴治疗的帕金森病患者出现反应波动的原因尚不清楚。在一些患者中，很难确定左旋多巴剂量和给药时间与所产生的临床效果之间的明确关系。这可能是由于药物吸收程度的差异，以及从摄入到血浆峰值水平以及从血浆峰值到中枢作用的潜伏期的差异。在所展示的一名患者中，对“开-关”图表的仔细分析揭示了在仅根据病史提示对左旋多巴有完全随机反应的时间点存在剂量末期恶化的潜在模式。在三名患者中，通过持续静脉输注左旋多巴并口服脱羧酶抑制剂来替代口服治疗，即使在患者行走时也产生了持久而稳定的临床反应。这种反应不仅在一名表现出可预测波动的患者中得以维持，而且在两名对口服治疗反应不可预测的患者中也得以维持。当第一名患者尽管服用了大剂量的口服左旋多巴和脱羧酶抑制剂但仍经历长时间的“关”期时，在其常规口服治疗方案中添加静脉输注左旋多巴也产生了稳定的临床益处。这些结果表明，即使在反应波动复杂的患者中，只要左旋多巴能够以恒定速率并以足够的量输送到大脑，中枢多巴胺受体仍可用于刺激。
