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AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives

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Abstract

Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.

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Authors and Affiliations

  1. Division of Bioequivalence, Office of Generic Drugs, Food and Drug Administration, Rockville, MD, USA

    Chandra S. Chaurasia

  2. Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria

    Markus Müller & Christian Joukhadar

  3. Division of Clinical Pharmacology III, Office of Clinical Pharmacology, US-FDA, Silver Spring, MD, USA

    Edward D. Bashaw

  4. Department of Dermatology, University of Copenhagen, Copenhagen, Denmark

    Eva Benfeldt

  5. Deptartment of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden

    Jan Bolinder

  6. Medical College of Virginia, Richmond, VA, USA

    Ross Bullock

  7. Division of Bioengineering and Physical Science, Office of Research Services, NIH, Bethesda, MD, USA

    Peter M. Bungay

  8. LACDR, Leiden, The Netherlands

    Elizabeth C. M. DeLange

  9. Department of Pharmaceutics, University of Florida, Gainesville, FL, USA

    Hartmut Derendorf

  10. Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA

    William F. Elmquist, Ronald J. Sawchuk & Belinda W. Y. Cheung

  11. Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  12. Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Dean L. Kellogg Jr.

  13. Department of Chemistry, University of Kansas, Lawrence, KS, USA

    Craig E. Lunte

  14. Department of Neurosurgery, University Hospital, Lund, Sweden

    Carl Henrik Nordstrom

  15. Department Neuroscience, Pfizer Global Research, Groton, CT, USA

    Hans Rollema

  16. Pharmaceutical Federation, North Potomac, MD, USA

    Vinod P. Shah

  17. Astra Zeneca, Södertälje, Sweden

    Lars Stahle

  18. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Urban Ungerstedt

  19. Pharmacokinetics and Drug Metabolism, Allergan Inc., Irvine, CA, USA

    Devin F. Welty

  20. Departnment of Drug Metabolism and Pharmacokinetics, Roche Palo Alto, CA, USA

    Helen Yeo

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  1. Chandra S. Chaurasia
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Correspondence to Chandra S. Chaurasia.

Additional information

The views expressed in this paper are those of the authors and do not necessarily reflect the opinions of their companies/institutions or the official policy of the FDA. No official support or endorsement by the FDA is intended or should be inferred. The contents of this report were presented by the authors at the Microdialysis Workshop, Nashville, TN, Nov 4–5, 2005 organized by American Association of Pharmaceutical Scientists and Co-Sponsored with the US Food and Drug Administration.

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Chaurasia, C.S., Müller, M., Bashaw, E.D. et al. AAPS-FDA Workshop White Paper: Microdialysis Principles, Application and Regulatory Perspectives. Pharm Res 24, 1014–1025 (2007). https://doi.org/10.1007/s11095-006-9206-z

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