In Vivo Electrochemical Monitoring of Safinamide Pharmacokinetics in the Brain Explores Its Correlation With Vision-Related Neuronal Activity.

Research overview

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Understanding drug pharmacokinetics (PK) at its site of action, particularly in the brain, is essential for accurately evaluating therapeutic efficacy and safety. However, conventional PK assessment based on blood measurements often fails to reflect drug dynamics in the central nervous system (CNS). Here, taking the anti-Parkinson's drug safinamide (SAF) as an example, we introduce a real-time in vivo electrochemical sensing strategy with high spatiotemporal resolution, operational simplicity, and excellent reproducibility. Our results reveal that the PK profile of SAF in the substantia nigra (SN) differs markedly from that in plasma, characterized by enhanced brain accumulation and distinct clearance kinetics. By simultaneously monitoring SAF and neuronal activity in the superficial gray layer (SuG) of the superior colliculus (SC), we observed pronounced suppression of neuronal firing at peak SAF levels, followed by gradual recovery during SAF elimination. This tight temporal correlation suggests that transient inhibition of vision-related neuronal activity may be directly associated with SAF concentration at the site. Overall, our study establishes an electrochemical approach enabling rapid, selective, and real-time drug monitoring in the living brain, offering a powerful tool to promote mechanistic studies of CNS drug action and safety.

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