The Real-Time Application of Control Theory to Pharmacokinetics

An optically-based injection control system has been developed as a proof-of- concept that such is of use for an intravenous drug delivery application. Current clinical drug delivery for oncology typically provides for intravenous administration without providing awareness of achieved plasma concentration, yet interpatient variability produces consequences ranging from toxicity to ineffectual treatments. We report a closed loop injection system integrating a pulse-photoplethysmograph to measure the concentration of indocyanine green (ICG) in the circulating blood of a one-compartment murine model. A proportional-derivative (PD) controller manages the injection rate in real-time. The target function for the controller is the population estimate of the pharmacokinetic model developed using Bayesian statistics describing the injection phase of a calibration set of 22 injections in mice. The controlled set of 8 injections showed a reduction in variance from the target injection phase concentration profile of 74.8%