Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration.
Non-Invasive Sweat-Based Tracking of L-Dopa Pharmacokinetic Profiles Following an Oral Tablet Administration.
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DOI：
10.1002/anie.202106674
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发表时间：
2021-08-23
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Moon JM;Teymourian H;De la Paz E;Sempionatto JR;Mahato K;Sonsa-Ard T;Huang N;Longardner K;Litvan I;Wang J
左旋多巴(L-多巴)是帕金森病(PD)对症治疗的黄金标准药物。然而，长期使用L-多巴会导致运动和非运动并发症的发生，这主要是由于其血浆水平的波动与疾病的进展有关。在此，我们提供了首例受试者在服用标准L-多巴口服丸后进行个体化治疗药物监测的例子，重点是动态跟踪指端自然分泌汗液中的药物浓度。这种基于触摸的非侵入性检测方法依赖于指尖汗液在高渗透性水凝胶上的瞬时收集，该水凝胶将汗液传输到生物催化酪氨酸酶修饰的电极上，在电极上通过还原多巴醌酶产物来测量汗液L-多巴。在一组受试者中，显示了个性化的剂量-反应关系，以及基于手指触摸的指尖汗液和毛细血管血液样本之间的密切药代动力学相关性。这种新的检测方法消除了对频繁采血的需要，并为帕金森病患者创造优化的、个性化的治疗方案带来了巨大的希望。非侵入性的基于触摸的汗液测量用于跟踪单剂量口服片剂后左旋多巴的药代动力学。
Levodopa (L-Dopa) is the ‘gold-standard’ medication for symptomatic therapy of Parkinson disease (PD). However, L-Dopa long-term use is associated with the development of motor and non-motor complications, primarily due to its fluctuating plasma levels in combination with the disease progression. Herein, we present the first example of individualized therapeutic drug monitoring for subjects upon intake of standard L-Dopa oral pill, centered on dynamic tracking of the drug concentration in naturally secreted fingertip sweat. The touch-based non-invasive detection method relies on instantaneous collection of fingertip sweat on a highly permeable hydrogel that transports the sweat to a biocatalytic tyrosinase-modified electrode, where sweat L-Dopa is measured by reduction of the dopaquinone enzymatic product. Personalized dose-response relationship is demonstrated within a group of human subjects, along with close pharmacokinetic correlation between the finger touch-based fingertip sweat and capillary blood samples. The new detection method obviates the need for frequent blood sampling and holds considerable promise for creating optimized, personalized therapeutic regimens for individuals with PD. Non-invasive touch-based sweat measurements are used for tracking the pharmacokinetic profiles of levodopa following a single-dose oral tablet administration.
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