High-Precision Control of Plasma Drug Levels Using Feedback-Controlled Dosing

By, in effect, rendering pharmacokinetics an experimentally adjustable parameter, the ability to perform feedback-controlled dosing informed by high-frequency in vivo drug measurements would prove a powerful tool for both pharmacological research and clinical practice. Efforts to this end, however, have historically been thwarted by an inability to measure in vivo drug levels in real time and with sufficient convenience and temporal resolution. In response, we describe a closed-loop, feedback-controlled delivery system that uses drug level measurements provided by an in vivo electrochemical aptamer-based (E-AB) sensor to adjust dosing rates every 7 s. The resulting system supports the maintenance of either constant or predefined time-varying plasma drug concentration profiles in live rats over many hours. For researchers, the resultant high-precision control over drug plasma concentrations provides an unprecedented opportunity to (1) map the relationships between pharmacokinetics and clinical outcomes, (2...