Biosensor Strip for Rapid On‐site Assessment of Levodopa Pharmacokinetics along with Motor Performance in Parkinson's Disease

• Published in: Angewandte Chemie International Edition 2024-07, Vol.63 (27), p.e202403583-n/a
• Main Authors: Mahato, Kuldeep, Moon, Jong‐Min, Moonla, Chochanon, Longardner, Katherine, Ghodsi, Hamidreza, Litvan, Irene, Wang, Joseph
• Format: Article
• Language: English
• Subjects: biosensor; Biosensors; Blood; Blood levels; Dosage; Dyskinesia; Fluctuations; Levodopa; levodopameter; levodopastrip; Liquid chromatography; Motor task performance; Movement disorders; near-realtime TDM; Neurodegenerative diseases; Parkinson's disease; parkinsons management; Pharmacokinetics; Plasma levels; Quality of life; Signs and symptoms; Strip; Symptom management
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202403583

While levodopa (L‐Dopa) is the primary treatment for alleviating Parkinson's disease (PD), its efficacy is hindered by challenges such as a short half‐life and inconsistent plasma levels. As PD progresses, the rising need for increased and more frequent L‐Dopa doses coupled with symptom fluctuations and dyskinesias underscores the urgency for improved comprehension of the interplay between L‐Dopa levels and PD motor symptoms. Addressing this critical need, we present a decentralized testing method using a disposable biosensor strip and a universal slope (U‐slope) calibration‐free approach. This enables reliable, rapid, simple, and cost‐effective decentralized L‐Dopa measurements from capillary blood. A pilot study with PD persons demonstrates the ability to monitor real‐time L‐Dopa pharmacokinetics from fingerstick blood after oral L‐Dopa‐Carbidopa (C–Dopa) tablet administration. Correlating capillary blood L‐Dopa levels with PD motor scores revealed a well‐defined inverse correlation with temporal motor fluctuations. We compared the resulting dynamic capillary blood L‐Dopa levels with plasma L‐Dopa levels using the traditional but clinically impractical high‐performance liquid chromatography technique. By providing timely feedback on a proper L‐Dopa dosing regimen in a decentralized and rapid fashion, this new biosensing platform will facilitate tailored optimal L‐Dopa dosing, towards improving symptom management and enhancing health‐related quality of life. The ability to monitor L‐Dopa levels on the spot reliably, rapidly, and inexpensively in outpatient settings, is demonstrated using disposable biosensor strips. The resulting hand‐held calibration‐free L‐Dopameter system offers near real‐time tracking of temporal L‐Dopa blood profiles in Parkinson patients following a single‐dose oral tablet administration. Such L‐Dopa blood profiles correlate closely with the corresponding motor response trends.