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Front Mol Biosci. 2019 Aug 16;6:69. doi: 10.3389/fmolb.2019.00069. eCollection 2019.

Ultra-High-Precision, in-vivo Pharmacokinetic Measurements Highlight the Need for and a Route Toward More Highly Personalized Medicine.

Author information

1
Department of Psychology, California State University, Dominguez Hills, Carson, CA, United States.
2
Institute for Collaborative Biotechnologies, University of California, Santa Barbara, Santa Barbara, CA, United States.
3
Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, United States.
4
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
5
Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, United States.
6
Center for Bioengineering, University of California, Santa Barbara, Santa Barbara, CA, United States.
7
Bren School of Environmental Science & Management, University of California, Santa Barbara, Santa Barbara, CA, United States.
8
Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, Santa Barbara, CA, United States.
9
Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, United States.
10
Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, United States.

Abstract

Clinical drug dosing would, ideally, be informed by high-precision, patient-specific data on drug metabolism. The direct determination of patient-specific drug pharmacokinetics ("peaks and troughs"), however, currently relies on cumbersome, laboratory-based approaches that require hours to days to return pharmacokinetic estimates based on only one or two plasma drug measurements. In response clinicians often base dosing on age, body mass, pharmacogenetic markers, or other indirect estimators of pharmacokinetics despite the relatively low accuracy of these approaches. Here, in contrast, we explore the use of indwelling electrochemical aptamer-based (E-AB) sensors as a means of measuring pharmacokinetics rapidly and with high precision using a rat animal model. Specifically, measuring the disposition kinetics of the drug tobramycin in Sprague-Dawley rats we demonstrate the seconds resolved, real-time measurement of plasma drug levels accompanied by measurement validation via HPLC-MS on ex vivo samples. The resultant data illustrate the significant pharmacokinetic variability of this drug even when dosing is adjusted using body weight or body surface area, two widely used pharmacokinetic predictors for this important class of antibiotics, highlighting the need for improved methods of determining its pharmacokinetics.

KEYWORDS:

aminoglycosides; aptamer-based sensors; body surface area; pharmacokinetics; therapeutic drug monitoring

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