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In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans

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Drug Transporters

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 201))

Abstract

Intestinal P-glycoprotein (P-gp, ABCB1) may significantly influence drug absorption and elimination. Its expression and function is highly variable, regio-selective and influenced by genetic polymorphisms, drug interactions and intestinal diseases. An in vivo probe drug for intestinal P-gp should a registered, safe and well tolerated nonmetabolized selective substrate with low protein binding for which P-gp is rate-limiting during absorption. Other P-gp dependent processes should be of minor influence. The mechanism(s) and kinetics of intestinal uptake must be identified and quantified. Moreover, the release properties of the dosage form should be known. So far, the cardiac glycoside digoxin and the ß1-selective blocker talinolol have been used in mechanistic clinical studies, because they meet most of these criteria. Digoxin and talinolol are suitable in vivo probe drugs for intestinal P-gp under the precondition, that they are used as tools in carefully designed pharmacokinetic studies with adequate biometrically planning of the sample size and that several limitations are considered in interpreting and discussion of the study results.

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Authors and Affiliations

  1. Department of Clinical Pharmacology, University of Greifswald, Friedrich-Loeffler-Str. 23d, 17487, Greifswald, Germany

    Stefan Oswald & Werner Siegmund

  2. AWD.pharma GmbH & Co. KG, Wasastr. 50, 01445, Radebeul, Dresden, Germany

    Bernd Terhaag

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  1. Stefan Oswald
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  2. Bernd Terhaag
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  3. Werner Siegmund
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Correspondence to Werner Siegmund .

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  1. Inst. Experimentelle und Klinische, Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstr. 17, Erlangen, 91054, Germany

    Martin F. Fromm

  2. Division of Clinical Pharmacology, University of Western Ontario, Windmere Road 339, London, N6A 5A5, Ontario, Canada

    Richard B. Kim

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Oswald, S., Terhaag, B., Siegmund, W. (2011). In Vivo Probes of Drug Transport: Commonly Used Probe Drugs to Assess Function of Intestinal P-glycoprotein (ABCB1) in Humans. In: Fromm, M., Kim, R. (eds) Drug Transporters. Handbook of Experimental Pharmacology, vol 201. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14541-4_11

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