Leta Valentina, Klingelhoefer Lisa, Longardner Katherine, Campagnolo Marta, Levent Hafize Çotur, Aureli Federico, Metta Vinod, Bhidayasiri Roongroj, Chung-Faye Guy, Falup-Pecurariu Cristian, Stocchi Fabrizio, Jenner Peter, Warnecke Tobias, Ray Chaudhuri K
Parkinson's Foundation Center of Excellence at King's College Hospital, London, UK.
Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute, King's College London and National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre, Institute of Psychology, Psychiatry and Neurosciences, King's College London, London, UK.
Eur J Neurol. 2023 May;30(5):1465-1480. doi: 10.1111/ene.15734. Epub 2023 Mar 7.
Levodopa is the gold standard for the symptomatic treatment of Parkinson's disease (PD). There are well documented motor and non-motor fluctuations, however, that occur almost inevitably once levodopa is started after a variable period in people with PD. Whilst brain neurodegenerative processes play a part in the pathogenesis of these fluctuations, a range of barriers across the gastrointestinal (GI) tract can alter levodopa pharmacokinetics, ultimately contributing to non-optimal levodopa response and symptoms fluctuations. GI barriers to levodopa transport and absorption include dysphagia, delayed gastric emptying, constipation, Helicobacter pylori infection, small intestinal bacterial overgrowth and gut dysbiosis. In addition, a protein-rich diet and concomitant medication intake can further alter levodopa pharmacokinetics. This can result in unpredictable or sub-optimal levodopa response, 'delayed on' or 'no on' phenomena. In this narrative review, we provided an overview on the plethora of GI obstacles to levodopa transport and absorption in PD and their implications on levodopa pharmacokinetics and development of motor fluctuations. In addition, management strategies to address GI dysfunction in PD are highlighted, including use of non-oral therapies to bypass the GI tract.
左旋多巴是帕金森病（PD）症状性治疗的金标准。然而，有充分的文献记载，在PD患者开始使用左旋多巴后的一段可变时期内，几乎不可避免地会出现运动和非运动波动。虽然脑部神经退行性过程在这些波动的发病机制中起一定作用，但胃肠道（GI）的一系列屏障会改变左旋多巴的药代动力学，最终导致左旋多巴反应不佳和症状波动。左旋多巴转运和吸收的胃肠道屏障包括吞咽困难、胃排空延迟、便秘、幽门螺杆菌感染、小肠细菌过度生长和肠道菌群失调。此外，富含蛋白质的饮食和同时服用的药物会进一步改变左旋多巴的药代动力学。这可能导致不可预测或不理想的左旋多巴反应、“延迟开启”或“无开启”现象。在这篇叙述性综述中，我们概述了PD中左旋多巴转运和吸收的大量胃肠道障碍及其对左旋多巴药代动力学和运动波动发展的影响。此外，还强调了处理PD中胃肠道功能障碍的管理策略，包括使用非口服疗法绕过胃肠道。
