Identification and Evaluation of Clinical Substrates of Organic Anion Transporting Polypeptides 1B1 and 1B3.

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2019
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Abstract
Organic anion transporting polypeptides (OATPs) 1B1 and 1B3 facilitate the uptake of drugs and endogenous compounds into the liver. In recent years, the impact of these transporters on drug-drug interactions (DDIs) has become a focus of research, and the evaluation of their role in drug disposition is recommended by regulatory agencies worldwide. Although sensitive substrates of OATP1B1/1B3 have been identified in the literature and probe drugs have been proposed by regulatory agencies, there is no general consensus on the ideal in vivo substrate for clinical DDI studies as analysis may be confounded by contribution from other metabolic and/or transport pathways. A thorough analysis of the available in vitro and in vivo data regarding OATP1B1/1B3 substrates was performed using the in vitro, clinical, and pharmacogenetic modules in the University of Washington Drug Interaction Database. A total of 34 compounds were identified and further investigated as possible clinical substrates using a novel indexing system. By analyzing the compounds for in vivo characteristics, including sensitivity to inhibition by known OATP1B1/1B3 inhibitors, selectivity for OATP1B1/1B3 compared with other transport and metabolic pathways, and safety profiles, a total of six compounds were identified as potential clinical markers of OATP1B1/1B3 activity.
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mcfeely2019identificationclinical Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors McFeely, Savannah J;Ritchie, Tasha K;Yu, Jingjing;Nordmark, Anna;Levy, René H;Ragueneau-Majlessi, Isabelle;
Journal clinical and translational science
Year 2019
DOI
10.1111/cts.12623
URL
Keywords
sustainability interviews knowledge translation focus groups barriers implementation science dissemination health services research facilitators evidence-informed practice

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