Seconds-Resolved Measurements of Vancomycin Transport from the Plasma to the Interstitial Fluid Highlight a Path Towards Real-Time Therapeutic Drug Monitoring.

Continuous, in vivo drug and biomarker measurements could transform healthcare, enabling both the high-precision personalization of drug dosing and the real-time monitoring of health status. A practical realization of this vision, however, requires an improved understanding of the relationship between concentrations measured in the easily accessible dermal interstitial fluid (ISF) that correlate with the plasma concentrations that guide clinical decision making. As a preliminary step towards this goal, here we have used electrochemical, aptamer-based (EAB) sensors to perform seconds-resolved vancomycin measurements in the plasma and subcutaneous ISF of live rats. Concentrations of the antibiotic in the ISF vary rather little between different subcutaneous sites and, after the very rapid initial distribution phase is complete, they are well correlated with the plasma concentrations (mean R2 = 0.88). Likewise, a simple, two-compartment, two-parameter model describes our six paired plasma and ISF drug time courses quantitatively. Together, these findings provide further evidence of the viability of the drug concentration measurements performed in the subcutaneous or dermal ISF as a less invasive approach to real-time drug monitoring in individual patients.