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At present, many patients are medicated with various drugs, which are, at the same time, associated with an increased risk of drug--drug interactions (DDIs). Detailed analysis of mechanisms underlying DDIs is the basis of a better prediction of adverse drug events caused by drug interactions. In the last few decades, an involvement of transporters in such processes has been more and more recognized. Indeed, uptake transporters belonging to the organic anion-transporting polypeptide (OATP) family have been shown to interact with a variety of drugs in clinical use. Particularly, the subfamily of OATP1B transporters has been extensively studied, identifying several clinical significant DDIs based on those hepatic uptake transporters. By contrast, the role of OATP2B1 in this context is rather underestimated. Therefore, in addition to known interactions based on OATP1B transporters, we have focused on DDIs probably based on OATP2B1 inhibition in the liver and those possibly owing to the inhibition of OATP2B1-mediated drug absorption in the intestine. [ABSTRACT FROM AUTHOR]

ATP-binding cassette(ABC) transporters comprise one of the largest membrane bound protein families. They are involved in transport of numerous compounds. These proteins transport substrates against a concentration gradient with ATP hydrolysis as a driving force across the membrane. Mammalian ABC proteins have important physiological, pharmacological and toxicological functions including the transport of lipids, bile salts, drugs, toxic and environmental agents. The efflux pumps serve both as natural defense mechanisms and influence the bioavailability and disposition of drugs. In general terms, the transporters remove xenobiotics from the cellular environment. For example, in cancer cells, over expression of these molecules may confer to multidrug resistance against cytostatic drugs. In addition, based on diverse structural characteristics and a broad substrate specifity, ABC transport proteins alter the intracellular concentration of a variety of therapeutically used compounds and toxicologically relevant agents. We review the function of the human multidrug resistance protein MDR1,(P-glycoprotein, ABCB1) and the multidrug resistance protein MRP2(ABCC2). We focus on four topics namely 1) structure and physiological functions of these transporters, 2) substrates e.g., drugs, xenotoxins, and environmental toxicants including their conjugates, 3) drug–drug interactions, and the role of chemosensitizers which may be able to reverse drug resistance, and 4) pharmacologically and toxicologically relevant genetic polymorphisms in transport proteins and their clinical implications. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article about first-in-human clincial trial in the December 9, 2016 issue.