a Department of Neurology , St. Joseph Hospital Berlin-Weißensee , Berlin , Germany.
Expert Opin Pharmacother. 2018 Jun;19(9):1003-1011. doi: 10.1080/14656566.2018.1484108. Epub 2018 Jun 18.
Parkinson's disease is a chronic, neurodegenerative disease. Its symptoms and course are heterogeneous. After several years of investigative drug studies, levodopa remains the most efficacious drug despite its long-term limitations. Consequently, research into new drug delivery modes is ongoing.
This review summarizes past and current advances of levodopa therapy with a focus on long-term patient management. Current research aims to increase drug bioavailability and to deliver it to the brain continuously. Reduced fluctuations improve drug efficacy and levodopa-associated motor complications. Less considered metabolic long-term consequences of levodopa are impaired methylation capacity and antioxidant defense. Both may contribute to disease progression and weaken physiological available human neuronal repair mechanisms.
New developed formulations will improve pharmacokinetic and pharmacodynamic behavior. The authors suggest the regular supplementation with methyl group-donating and free radical scavenging substrates to weaken the metabolic consequences of chronic and high levodopa dosing. Many patients perform this nutrient supplementation in their diet already.
帕金森病是一种慢性神经退行性疾病。其症状和病程存在异质性。经过多年的研究药物治疗,左旋多巴仍然是最有效的药物,尽管它存在长期的局限性。因此,正在进行新的药物输送模式的研究。
本综述总结了过去和目前左旋多巴治疗的进展,重点关注长期患者管理。目前的研究旨在提高药物的生物利用度,并持续将其输送到大脑。减少波动可提高药物疗效和与左旋多巴相关的运动并发症。较少考虑到的左旋多巴的代谢长期后果是甲基化能力和抗氧化防御受损。这两者都可能导致疾病进展并削弱生理上可用的人类神经元修复机制。
新开发的制剂将改善药代动力学和药效学行为。作者建议定期补充提供甲基供体和自由基清除剂的物质,以减弱慢性和高剂量左旋多巴给药的代谢后果。许多患者已经在饮食中进行这种营养补充。