B-301 In-vivo Continuous Therapeutic Drug Monitoring With Electrochemical Aptamer-based Sensors

Abstract

Abstract Therapeutic drug monitoring (TDM) is a clinical practice involving quantification of plasma drug concentrations to adjust treatment efficacy and minimize toxicity in patient care. TDM is relevant for drugs with a narrow therapeutic index, defined as the plasma concentration range over which a molecule is therapeutically effective without causing significant adverse effects. For narrow therapeutic index drugs, indirect predictors of a patient’s metabolism, such as age, body mass, or genotype, are insufficient to ensure effective dosing, and metabolic variability across different individuals needs to be considered. The importance of TDM is illustrated by the difficulty in treating a patient with vancomycin, an essential antibiotic used to combat gram-positive bacterial infections. The practice typically involves determining trough concentration, peak concentration, or exposure to the vancomycin area under the curve, necessitating blood sampling. After sampling, the current practices require patient blood to be sent to a laboratory, which can only provide an answer from hours after sample collection. Electrochemical aptamer-based (E-AB) sensors provide significant opportunities to make TDM a practice as frequent and convenient as the measurement of blood sugar has become for people with diabetes. This is because E-AB sensing is a molecular approach to continuously measuring concentrations of specific molecules. We present the selection of an aptamer against vancomycin and its adaptation into an E-AB sensor. Using this sensor, we then demonstrate the opportunities for rapid (seconds) measurement of plasma vancomycin and the real-time measurement of subject-specific vancomycin pharmacokinetics on rats (Fig. 1) [3]. Such capability provides a route toward improving TDM and the personalized delivery of pharmacological interventions.Fig. 1.Real-time continuous monitoring of subject-specific vancomycin pharmacokinetics with electrochemical aptamer-based sensors. Reprinted with permission from the American Chemical Society.