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Role of extracellular vesicle derived biomarkers in drug metabolism and disposition

Zivile Useckaite, A. David Rodrigues, Ashley M Hopkins, Lauren A Newman, Jillian G Johnson, Michael J Sorich and Andrew Rowland
Drug Metabolism and Disposition August 5, 2021, DMD-MR-2021-000411; DOI: https://doi.org/10.1124/dmd.121.000411
Zivile Useckaite
1Flinders University, Australia
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A. David Rodrigues
2Drug Metabolism and Pharmacokinetics, Pfizer, United States
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Ashley M Hopkins
1Flinders University, Australia
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Lauren A Newman
1Flinders University, Australia
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Jillian G Johnson
3Pfizer, United States
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Michael J Sorich
1Flinders University, Australia
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  • ORCID record for Michael J Sorich
Andrew Rowland
4Clinical Pharmacology, Flinders University, Australia
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  • For correspondence: andrew.rowland@flinders.edu.au
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Abstract

Extracellular vesicles (EVs) are small, non-replicating, lipid encapsulated particles that contain a myriad of protein and nucleic acid cargo derived from their tissue of origin. The potential role of EV derived biomarkers to the study of drug metabolism and disposition (DMD) has gained attention in recent years. The key trait that makes EVs an attractive biomarker source is their capacity to provide comparable insights to solid organ biopsy through an appreciably less invasive collection procedure. Blood-derived EVs exist as a heterogenous milieu of biologically distinct particles originating from different sources through different biogenesis pathways. Furthermore, blood (plasma and serum) contains an array of vesicular and non-vesicular contaminants such as apoptotic bodies, plasma proteins and lipoproteins that are routinely co-isolated with EVs albeit to a different extent depending on the isolation technique. The following mini-review summarises current studies reporting DMD biomarkers and addresses elements of EV isolation and quantification relevant to the application of EV derived DMD biomarkers. Evidence based best practice guidance aligned to Minimum Information for the Study of Extracellular Vesicles (MISEV) and EV Track reporting standards are summarised in the context of DMD studies.

Significance Statement Extracellular vesicle (EV) derived protein and nucleic acid cargo represent a potentially game changing source of novel DMD biomarkers with the capacity to define within- and between- individual variability in drug exposure irrespective of aetiology. However, robust translation of EV-derived biomarkers requires the generation of transparent reproducible evidence. This review outlines the critical elements of data generation and reporting relevant to achieving this evidence in a drug metabolism and disposition context.

  • Cytochrome P450 (CYP)
  • drug metabolism
  • glucuronidation/UDP-glucuronyltransferases/UGT
  • transporters
  • Copyright © 2020 American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 50 (6)
Drug Metabolism and Disposition
Vol. 50, Issue 6
1 Jun 2022
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EV Biomarkers in DMD

Zivile Useckaite, A. David Rodrigues, Ashley M Hopkins, Lauren A Newman, Jillian G Johnson, Michael J Sorich and Andrew Rowland
Drug Metabolism and Disposition August 5, 2021, DMD-MR-2021-000411; DOI: https://doi.org/10.1124/dmd.121.000411

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OtherMinireview

EV Biomarkers in DMD

Zivile Useckaite, A. David Rodrigues, Ashley M Hopkins, Lauren A Newman, Jillian G Johnson, Michael J Sorich and Andrew Rowland
Drug Metabolism and Disposition August 5, 2021, DMD-MR-2021-000411; DOI: https://doi.org/10.1124/dmd.121.000411
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