Membrane transporters in drug development and as determinants of precision medicine

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. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.

Brouwer, Kim L. R. (author)
Tweedie, Donald (author)
Yoshida, Kenta (author)
Sjostedt, Noora (author)
Aleksunes, Lauren (author)
Chu, Xiaoyan (author)
Evers, Raymond (author)
Hafey, Michael J. (author)
Lai, Yurong (author)
Matsson, Pär,1978Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xmatsp (author)
Riselli, Andrew (author)
Shen, Hong (author)
Sparreboom, Alex (author)
Varma, Manthena V. S. (author)
Yang, Jia (author)
Yang, Xinning (author)
Yee, Sook Wah (author)
Zamek-Gliszczynski, Maciej J. (author)
Zhang, Lei (author)
Giacomini, Kathleen M. (author)
Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för farmakologi (creator_code:org_t)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

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