A skin-interfaced sensor for noninvasive monitoring of pharmacokinetic and pharmacodynamic responses

Interindividual and intraindividual variations in physiology critically affect the interactions between therapeutic drugs and the human body, posing challenges to precision medicine in both daily life and specialized settings. Noninvasive wearable sensors that can dynamically and simultaneously track pharmacokinetic (PK) responses and corresponding pharmacodynamic (PD) changes could address this need but remain largely unexplored. Here, we present P²One, a skin-interfaced epidermal sensor for real-time, noninvasive monitoring of PK and PD biomarkers in sweat. Using metformin (a widely prescribed drug for type 2 diabetes) as a model, P²One with high performance on metformin (linearity of 10 nM to 10 μM and detection limit of 1.16 nM at a signal-to-noise ratio of 3) and glucose analysis (linearity of 5-300 μM and detection limit of 4.15 μM at a signal-to-noise ratio of 3) enables in situ and simultaneous measurement of sweat metformin and glucose. In human trials, we demonstrate real-time monitoring of drug absorption and excretion under controlled conditions. In diabetic patients, we evaluate the clinical utility of P²One for personalized metformin therapy, by correlating plasma and sweat metformin as well as blood and sweat glucose over a four-week oral administration regimen. These results establish a wearable sensing strategy for PK- and PD-guided therapeutic drug monitoring, with potential applications in precision medicine across diverse environments.