Biomarkers for In Vivo Assessment of Transporter Function

Pharmacological Reviews
Fabian MüllerM F Fromm

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 cur...Continue Reading

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Citations

Jan 17, 2019·Clinical Pharmacology and Therapeutics·Arne GessnerMartin F Fromm
Mar 28, 2019·Clinical Pharmacology and Therapeutics·Aleksi TornioJanne T Backman
Oct 14, 2018·The Journal of Pharmacology and Experimental Therapeutics·Shelby BarnettAleksandra Galetin
Oct 27, 2018·The Journal of Pharmacology and Experimental Therapeutics·Hong ShenW Griffith Humphreys
Feb 16, 2020·American Journal of Hypertension·Panayiotis LoucaSandosh Padmanabhan
Jul 30, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yueping ZhangHong Shen
Sep 29, 2021·Clinical Pharmacology and Therapeutics·Mikko NeuvonenMikko Niemi
Oct 3, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jennifer TangYurong Lai
Aug 25, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jiayi YinSu Zeng

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