Bianchine J R, Shaw G M
Clin Pharmacokinet. 1976;1(5):313-38. doi: 10.2165/00003088-197601050-00001.
Although levodopa has provided a major advance in the treatment of parkinsonism, its maximum benefits have not yet been realised, in part because of its complicated pharmacokinetics. This review summarises that available pharmacokinetic data involving levodopa, especially as it relates to therapeutic response of parkinsonian patients. A large number of factors, including protein intake, gastric emptying time, pyridoxine ingestion, and dopa decarboxylase activity, affect plasma levels of levodopa attained following oral administration of this drug. Other variables influence the rate of brain uptake of levodopa from the blood. Even so, plasma levodopa concentration correlates significantly with dosage size in a large parkinsonian population and also coincides with therapeutic response in many, but not all, patients. Therefore, in certain instances, valuable information may be derived by correlating clinical response with plasma levodopa concentration. Cerebrospinal fluid levels of homovanillic acid, a major metabolite of dopamine, may have some value in predicting clinical response to levodopa. This relationship, however, has not been firmly established. Concentration of homovanillic acid or levodopa in body fluids may also be closely related to certain adverse side-effects, including abnormal involuntary movements, gastric discomfort and psychiatric disturbances. Evidence indicates that a clearer understanding of levodopa pharmacokinetics may improve the clinical management of parkinsonism.
尽管左旋多巴在帕金森病的治疗方面取得了重大进展，但其最大益处尚未完全实现，部分原因在于其复杂的药代动力学。本综述总结了现有的涉及左旋多巴的药代动力学数据，尤其是与帕金森病患者治疗反应相关的数据。大量因素，包括蛋白质摄入量、胃排空时间、吡哆醇摄入以及多巴脱羧酶活性，都会影响口服该药物后所达到的左旋多巴血浆水平。其他变量则影响左旋多巴从血液进入大脑的速率。即便如此，在大量帕金森病患者群体中，血浆左旋多巴浓度与剂量大小显著相关，并且在许多（但并非所有）患者中也与治疗反应相符。因此，在某些情况下，通过将临床反应与血浆左旋多巴浓度相关联，可能会获得有价值的信息。脑脊液中多巴胺的主要代谢产物高香草酸的水平，在预测对左旋多巴的临床反应方面可能具有一定价值。然而，这种关系尚未得到确凿证实。体液中高香草酸或左旋多巴的浓度也可能与某些不良副作用密切相关，包括异常的不自主运动、胃部不适和精神障碍。有证据表明，更清楚地了解左旋多巴药代动力学可能会改善帕金森病的临床管理。
