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Principal Investigator: Tod Edward Kippin
Organization: UNIVERSITY OF CALIFORNIA SANTA BARBARA
Fiscal Year: 2024
Award: $595,697
Funding agency: National Institute of Biomedical Imaging and Bioengineering
Summary. Our overarching goal is to render therapeutic drug monitoring as convenient and highly time resolved
as the continuous glucose monitor has rendered the monitoring of blood sugar. The realization of this goal would
transform many aspects of both biomedical research and clinical practice. It would, for example, enable
personalized dosing based on a patient’s accurately determined, rather than poorly predicted, drug metabolism,
an outcome of high relevance to the treatment of infectious diseases, which commonly employs drugs of
dangerously narrow therapeutic index, and to improving women’s health, as pharmacokinetic sex differences
lead to a doubling of adverse pharmacotherapeutic outcomes in females. Ultimately such a technology could
enable feedback-controlled drug dosing, which, by responding in real time to metabolic variations, would improve
the safety and efficacy of drugs that suffer from dose-limiting toxicity. To achieve our goal, however, requires
two significant innovations: (1) a technology able to monitor arbitrary drug molecules in situ in the intestinal fluid
(ISF) of the subcutaneous space and (2) vastly improved knowledge regarding how the pharmacokinetics of
drugs in the ISF relate to the pharmacokinetics seen in plasma. Under the prior round of grant funding, we
achieved the first of these necessary advances. Specifically, we demonstrated that minimally-invasive
Electrochemical, Aptamer-Based (EAB) sensors support the seconds-resolved, real-time measurement of drugs
in situ in the plasma (venous), cerebrospinal fluid (brain), and ISF (subcutaneous space) of our live rat animal
model. Here we propose to tackle the second innovation. That is, using intravenous and subcutaneous EAB
sensors we propose to advance understanding of the relationships between plasma and ISF pharmacokinetics
across a diverse set of antimicrobial and immunosuppressant drugs for which therapeutic drug monitoring is an
important element of the standard of care. We believe the resulting orders of magnitude improvement in
measuring these relationships is a critical step towards our long-range goal of rendering high-precision
therapeutic drug monitoring convenient and cost effective.
Terms: <Animal Model><Animal Models and Related Studies><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Area Under Curve><Biological Markers><Biomedical Research><Blood><Blood Glucose><Blood Plasma><Blood Reticuloendothelial System><Blood Sugar><Body Tissues><Brain><Brain Nervous System><Cerebrospinal Fluid><Chemicals><Clinical><Clinical Pharmacology><Common Rat Strains><Complex><Continuous Glucose Monitor><Dangerousness><Diabetes Mellitus><Differences between sexes><Differs between sexes><Dose><Dose Limiting><Drug Delivery><Drug Delivery Systems><Drug Exposure><Drug Kinetics><Drug Monitoring><Drug Transport><Drugs><Elements><Encephalon><Ensure><Feedback><Female Health><Funding><Goals><Grant><Health><Immunosuppressants><Immunosuppressive Agents><Immunosuppressive drug><Immunosuppressive treatment><In Situ><Intestinal><Intestines><Intravenous><Knowledge><Lead><Liquid substance><Measurement><Measures><Medication><Metabolic><Miscellaneous Antibiotic><Molecular><Monitor><Outcome><Patients><Pb element><Pharmaceutical Preparations><Pharmacokinetics><Pharmacological Study><Pharmacology Study><Plasma><Plasma Serum><Precision therapeutics><Property><Rat><Rats Mammals><Rattus><Regimen><Reporting><Research><Resolution><Reticuloendothelial System, Serum, Plasma><Safety><Sex Differences><Sexual differences><Solid><Specificity><Survey Instrument><Surveys><Technology><Therapeutic><Therapeutic Index><Time><Tissues><Toxic effect><Toxicities><Variant><Variation><Venous><Women's Health><anti-microbial><antimicrobial><aptamer><bio-markers><biologic marker><biomarker><bowel><cerebral spinal fluid><clinical decision-making><clinical practice><clinical relevance><clinically relevant><continuous blood glucose monitor><continuous blood sugar monitor><continuous glucose measurement><continuous sugar monitor><cost effective><detector><diabetes><drug disposition><drug efficacy><drug metabolism><drug/agent><female outcomes><fluid><heavy metal Pb><heavy metal lead><immune suppressive agent><immune suppressor><immunosuppressive substance><immunosuppressor><improved><in vivo><in vivo monitoring><infectious disease treatment><innovate><innovation><innovative><insight><liquid><minimally invasive><model of animal><outcomes among females><outcomes among women><outcomes in females><outcomes in women><precision therapies><precision treatment><resolutions><sensor><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><spinal fluid><standard of care><stem><subcutaneous><subdermal><temporal measurement><temporal resolution><time measurement><tool><wearable><wearable device><wearable electronics><wearable system><wearable technology><wearable tool><wearables><women's outcomes>