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Pharmaceutics 2017, 9(4), 43;

Revolutionizing Therapeutic Drug Monitoring with the Use of Interstitial Fluid and Microneedles Technology

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada
Department of Electrical and Computer Engineering, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada
Author to whom correspondence should be addressed.
Received: 30 August 2017 / Revised: 4 October 2017 / Accepted: 7 October 2017 / Published: 11 October 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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While therapeutic drug monitoring (TDM) that uses blood as the biological matrix is the traditional gold standard, this practice may be impossible, impractical, or unethical for some patient populations (e.g., elderly, pediatric, anemic) and those with fragile veins. In the context of finding an alternative biological matrix for TDM, this manuscript will provide a qualitative review on: (1) the principles of TDM; (2) alternative matrices for TDM; (3) current evidence supporting the use of interstitial fluid (ISF) for TDM in clinical models; (4) the use of microneedle technologies, which is potentially minimally invasive and pain-free, for the collection of ISF; and (5) future directions. The current state of knowledge on the use of ISF for TDM in humans is still limited. A thorough literature review indicates that only a few drug classes have been investigated (i.e., anti-infectives, anticonvulsants, and miscellaneous other agents). Studies have successfully demonstrated techniques for ISF extraction from the skin but have failed to demonstrate commercial feasibility of ISF extraction followed by analysis of its content outside the ISF-collecting microneedle device. In contrast, microneedle-integrated biosensors built to extract ISF and perform the biomolecule analysis on-device, with a key feature of not needing to transfer ISF to a separate instrument, have yielded promising results that need to be validated in pre-clinical and clinical studies. The most promising applications for microneedle-integrated biosensors is continuous monitoring of biomolecules from the skin’s ISF. Conducting TDM using ISF is at the stage where its clinical utility should be investigated. Based on the advancements described in the current review, the immediate future direction for this area of research is to establish the suitability of using ISF for TDM in human models for drugs that have been found suitable in pre-clinical experiments. View Full-Text
Keywords: clinical pharmacokinetics; therapeutic drug monitoring; interstitial fluid; microneedles clinical pharmacokinetics; therapeutic drug monitoring; interstitial fluid; microneedles

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kiang, T.K.; Ranamukhaarachchi, S.A.; Ensom, M.H. Revolutionizing Therapeutic Drug Monitoring with the Use of Interstitial Fluid and Microneedles Technology. Pharmaceutics 2017, 9, 43.

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