1. Membrane transporters in drug development and as determinants of precision medicine
- Author
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Galetin, Aleksandra, Brouwer, Kim LR, Tweedie, Donald, Yoshida, Kenta, Sjöstedt, Noora, Aleksunes, Lauren, Chu, Xiaoyan, Evers, Raymond, Hafey, Michael J, Lai, Yurong, Matsson, Pär, Riselli, Andrew, Shen, Hong, Sparreboom, Alex, Varma, Manthena VS, Yang, Jia, Yang, Xinning, Yee, Sook Wah, Zamek-Gliszczynski, Maciej J, Zhang, Lei, and Giacomini, Kathleen M
- Subjects
Pharmacology and Pharmaceutical Sciences ,Biomedical and Clinical Sciences ,Precision Medicine ,Patient Safety ,1.1 Normal biological development and functioning ,Infection ,Generic health relevance ,Humans ,Membrane Transport Proteins ,Drug Interactions ,Drug Development ,Biological Sciences ,Medical and Health Sciences ,Pharmacology & Pharmacy ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions.
- Published
- 2024