(449b) A Clinically Translatable Closed-Loop Drug Delivery System Can Personalize the Dosing of Multiple Chemotherapies

Patients are typically dosed on a body surface area (BSA) basis when receiving chemotherapies, which ignores many differences between patients including genetics, body composition, and sex differences. Incredibly, BSA is estimated using an equation from 1916 that was determined using data from just nine patients. The result of dosing on a BSA-basis is that many patients are either overdosed or under dosed, resulting in toxicity or worse therapeutic outcomes, respectively. Towards this end, we developed a closed loop drug delivery system that can personalize the dosing of a chemotherapy by measuring the concentration of the drug in real time, inputting that concentration into a control algorithm, and then adjusting the infusion rate to the patient. We call this system the Closed-Loop AUtomated Drug Infusion regulAtor (CLAUDIA). CLAUIA uses high-performance liquid chromatography-mass spectrometry (HPLC-MS) as the sensor, which allows CLAUDIA to be able to detect and control the concentration of a wide variety of different drugs with only making simple changes to the HPLC-MS method. We have demonstrated that CLAUDIA can control the concentration of 5-fluorouracil over a clinically relevant range of conditions in rabbits using an adaptive proportional, integral, derivative (PID) controller. We then designed another adaptive control algorithm that models a patient's pharmacokinetics and uses that information to update the parameters of the controller to allow it to function over a broad range of conditions that could be observed clinically. The advanced algorithm is capable of controlling the concentration of drugs over a wide range of half-lives in in silico simulations, and can control the concentration of both 5-fluorouracil and irinotecan in vivo in a rabbit model, demonstrating the ability of CLAUDIA to control the concentration of multiple different chemotherapies. Overall, CLAUDIA has the potential to personalize the dosing of a wide range of drugs, which could result in improved efficacy and decreased toxicity.