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Recent advances in understanding hepatic drug transport


Stieger, Bruno; Hagenbuch, Bruno (2016). Recent advances in understanding hepatic drug transport. F1000Research, 5:2465.

Abstract

Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo.

Abstract

Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes. Consequently, understanding the exact mechanisms of drug transporters is essential both in drug development and in drug therapy. While many drug transporters are expressed in hepatocytes, and some of them are well characterized, several transporters have only recently been identified as new drug transporters. Novel powerful tools to deorphanize (drug) transporters are being applied and show promising results. Although a large set of tools are available for studying transport in vitro and in isolated cells, tools for studying transport in living organisms, including humans, are evolving now and rely predominantly on imaging techniques, e.g. positron emission tomography. Imaging is an area which, certainly in the near future, will provide important insights into "transporters at work" in vivo.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2016
Deposited On:10 Nov 2016 16:00
Last Modified:02 Sep 2017 02:16
Publisher:Faculty of 1000 Ltd.
ISSN:2046-1402
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.12688/f1000research.9466.1
PubMed ID:27781095

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