Clinical Probes and Endogenous Biomarkers as Substrates for Transporter Drug-Drug Interaction Evaluation: Perspectives From the International Transporter Consortium

Xiaoyan Chu, Mingxiang Liao, Hong Shen, Kenta Yoshida, Arik A. Zur, Vikram Arya, Aleksandra Galetin, Kathleen M. Giacomini, Imad Hanna, Hiroyuki Kusuhara, Yurong Lai, David Rodrigues, Yuichi Sugiyama, Maciej J. Zamek-gliszczynski, Lei Zhang

Research output: Contribution to journalArticlepeer-review

854 Downloads (Pure)

Abstract

Drug transporters can govern the absorption, distribution, metabolism, and excretion of substrate drugs and endogenous substances. Investigations to examine their potential impact to pharmacokinetic (PK) drug‐drug interactions (DDIs) are an integral part of the risk assessment in drug development. To evaluate a new molecular entity as a potential perpetrator of transporters, use of well characterized and/or clinically relevant probe substrates with good selectivity and sensitivity are critical for robust clinical DDI assessment that could inform DDI management strategy in the product labeling. The availability of endogenous biomarkers to monitor transporter‐mediated DDIs in early phases of clinical investigations would greatly benefit downstream clinical plans. This article reviews the state‐of‐the‐art in transporter clinical probe drugs and emerging biomarkers, including current challenges and limitations, delineates methods and workflows to identify and validate novel endogenous biomarkers to support clinical DDI evaluations, and proposes how these probe drugs or biomarkers could be used in drug development.
Original languageEnglish
Pages (from-to)836-864
JournalClinical Pharmacology & Therapeutics
Volume104
Issue number5
Early online date22 Oct 2018
DOIs
Publication statusPublished - Nov 2018

Fingerprint

Dive into the research topics of 'Clinical Probes and Endogenous Biomarkers as Substrates for Transporter Drug-Drug Interaction Evaluation: Perspectives From the International Transporter Consortium'. Together they form a unique fingerprint.

Cite this