Biomarkers for In Vivo Assessment of Transporter Function

Mueller F, Sharma A, König J, Fromm M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Pharmacological Reviews American Society for Pharmacology and Experimental Therapeutics (ASPET)

Book Volume: 70

Pages Range: 246-277

Journal Issue: 2

DOI: 10.1124/pr.116.013326

Abstract

Drug-drug interactions are a major concern not only during clinical practice, but also in drug development. Due to limitations of in vitro-in vivo predictions of transporter-mediated drug-drug interactions, multiple clinical Phase I drug-drug interaction studies may become necessary for a new molecular entity to assess potential drug interaction liabilities. This is a resource-intensive process and exposes study participants, who frequently are healthy volunteers without benefit from study treatment, to the potential risks of a new drug in development. Therefore, there is currently a major interest in new approaches for better prediction of transporter-mediated drug-drug interactions. In particular, researchers in the field attempt to identify endogenous compounds as biomarkers for transporter function, such as hexadecanedioate, tetradecanedioate, coproporphyrins I and III, or glycochenodeoxycholate sulfate for hepatic uptake via organic anion transporting polypeptide 1B or N1-methylnicotinamide for multidrug and toxin extrusion protein-mediated renal secretion. We summarize in this review the currently proposed biomarkers and potential limitations of the substances identified to date. Moreover, we suggest criteria based on current experiences, which may be used to assess the suitability of a biomarker for transporter function. Finally, further alternatives and supplemental approaches to classic drug-drug interaction studies are discussed.

Authors with CRIS profile

Jörg König Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Martin Fromm Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie

Involved external institutions

Boehringer Ingelheim Pharma GmbH & Co. KG DE Germany (DE)

How to cite

APA:

Mueller, F., Sharma, A., König, J., & Fromm, M. (2018). Biomarkers for In Vivo Assessment of Transporter Function. Pharmacological Reviews, 70(2), 246-277. https://doi.org/10.1124/pr.116.013326

MLA:

Mueller, Fabian, et al. "Biomarkers for In Vivo Assessment of Transporter Function." Pharmacological Reviews 70.2 (2018): 246-277.

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