ABSTRACT Introduction: Parkinson’s disease is a chronic, neurodegenerative disease entity with heterogeneous features and course. Levodopa is the most efficacious dopamine substituting drug. Particularly, long-term application of oral levodopa/decarboxylase inhibitor formulations sooner or later supports onset of fluctuations of movement. It also shifts levodopa turnover to O-methylation, which impairs human methylation capacity and increases oxidative stress. Areas covered: This narrative review summarizes pharmacokinetic and pharmacodynamic features of available levodopa cotherapies on the basis of a literature search with the terms L-dopa, inhibitors of catechol-O-methyltransferase and monoamine oxidase-B. Expert opinion: Long-term levodopa/dopa decarboxylase inhibitor application with concomitant inhibition of both, catechol-O-methyltransferase and monoamine oxidase-B supports a more continuous dopamine substitution, which ameliorates fluctuations of motor behavior. This triple combination also enhances both, antioxidative defense and methylation capacity. Inhibition of monoamine oxidase-B reduces generation of oxidative stress in the brain. Constraint of catechol-O-methyltransferase reduces homocysteine synthesis due to diminished consumption of methyl groups for levodopa turnover at least in the periphery. An additional nutritional supplementation with methyl group donating and free radical scavenging vitamins is recommendable, when future drugs are developed for long-term levodopa/dopa decarboxylase treated patients. Personalized medicine treatment concepts shall also consider nutritional aspects of Parkinson’s disease.

中文翻译：

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左旋多巴/卡比多巴联合疗法治疗帕金森病的药代动力学和药效学

摘要 介绍：帕金森病是一种慢性、神经退行性疾病，具有异质特征和病程。左旋多巴是最有效的多巴胺替代药物。特别是，长期应用口服左旋多巴/脱羧酶抑制剂制剂迟早会支持运动波动的发生。它还将左旋多巴转换为 O-甲基化，这会损害人类甲基化能力并增加氧化应激。涵盖的领域：这篇叙述性综述基于对术语 L-多巴、儿茶酚-O-甲基转移酶抑制剂和单胺氧化酶-B 的文献搜索，总结了可用左旋多巴联合疗法的药代动力学和药效学特征。专家意见：长期应用左旋多巴/多巴脱羧酶抑制剂同时抑制两者，儿茶酚-O-甲基转移酶和单胺氧化酶-B 支持更连续的多巴胺替代，从而改善运动行为的波动。这种三重组合还增强了抗氧化防御和甲基化能力。抑制单胺氧化酶-B 可减少大脑中氧化应激的产生。儿茶酚-O-甲基转移酶的限制减少了同型半胱氨酸的合成，因为至少在外围的左旋多巴周转中甲基的消耗减少。当未来的药物被开发用于长期左旋多巴/多巴脱羧酶治疗的患者时，建议额外补充含有甲基基团和自由基清除维生素的营养补充剂。个性化药物治疗概念还应考虑帕金森病的营养方面。