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Absorption Models to Examine Bioavailability and Drug–Drug Interactions in Humans

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Enzyme- and Transporter-Based Drug-Drug Interactions

Abstract

Human drug absorption studies are warranted in many situations. The development of modified release formulations, the evaluation of different formulations designed to improve bioavailability by enhancing solubility or permeability, the investigation of mechanisms of drug-drug/food interactions in the gastro-intestinal tract, and the determination of intestinal and biliary secretion in humans all require assessment of drug absorption/excretion in the human gastrointestinal tract. This chapter discusses in vivo approaches that can be used to assess absorption/bioavailability issues in the human gastrointestinal tract. The design and the application of remotely activated capsules and aspiration/perfusion catheters are reviewed, and the utility of human microdose studies is discussed. With the use of appropriate probes, these approaches also may be used to assess drug–drug or drug–food interactions, as well as interactions involving transporters and enzymes present in the gastrointestinal tract and/or the liver.

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Acknowledgments

Dr. Brouwer’s research program is supported by grant R01 GM41935 from the National Institute of General Medical Sciences, National Institutes of Health. Ahsan N. Rizwan, M. Pharm., Ph.D. is a GlaxoSmithKline sponsored Clinical Pharmacokinetics and Pharmacodynamics Fellow at the UNC Eshelman School of Pharmacy, Division of Pharmacotherapy and Experimental Therapeutics.

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Authors and Affiliations

  1. Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Ahsan Naqi Rizwan & Kim L.R. Brouwer

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  1. Ahsan Naqi Rizwan
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  2. Kim L.R. Brouwer
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Correspondence to Kim L.R. Brouwer .

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Editors and Affiliations

  1. Leslie Dan Fac. Pharmacy, University of Toronto, College Street 144, Toronto, M5S 3M2, Canada

    K. Sandy Pang

  2. Bristol-Myers Squibb Company, Princeton, 08543, U.S.A.

    A. David Rodrigues

  3. AstraZeneca UK, Alderley Park, Macclesfield, Cheshire, SK10 4TF, United Kingdom

    Raimund M. Peter

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Rizwan, A.N., Brouwer, K.L. (2010). Absorption Models to Examine Bioavailability and Drug–Drug Interactions in Humans. In: Pang , K., Rodrigues, A., Peter, R. (eds) Enzyme- and Transporter-Based Drug-Drug Interactions. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0840-7_14

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