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dc.contributor.authorDurmus, S.en_US
dc.contributor.authorVan Hoppe, S.en_US
dc.contributor.authorSchinkel, A. H.en_US
dc.date.accessioned2018-04-12T10:55:36Z
dc.date.available2018-04-12T10:55:36Z
dc.date.issued2016en_US
dc.identifier.issn1368-7646
dc.identifier.urihttp://hdl.handle.net/11693/36854
dc.description.abstractIt is now widely accepted that organic anion-transporting polypeptides (OATPs), especially members of the OATP1A/1B family, can have a major impact on the disposition and elimination of a variety of endogenous molecules and drugs. Owing to their prominent expression in the sinusoidal plasma membrane of hepatocytes, OATP1B1 and OATP1B3 play key roles in the hepatic uptake and plasma clearance of a multitude of structurally diverse anti-cancer and other drugs. Here, we present a thorough assessment of the currently available OATP1A and OATP1B knockout and transgenic mouse models as key tools to study OATP functions in vivo. We discuss recent studies using these models demonstrating the importance of OATPs, primarily in the plasma and hepatic clearance of anticancer drugs such as taxanes, irinotecan/SN-38, methotrexate, doxorubicin, and platinum compounds. We further discuss recent work on OATP-mediated drug–drug interactions in these mouse models, as well as on the role of OATP1A/1B proteins in the phenomenon of hepatocyte hopping, an efficient and flexible way of liver detoxification for both endogenous and exogenous substrates. Interestingly, glucuronide conjugates of both the heme breakdown product bilirubin and the protein tyrosine kinase-targeted anticancer drug sorafenib are strongly affected by this process. The clinical relevance of variation in OATP1A/1B activity in patients has been previously revealed by the effects of polymorphic variants and drug–drug interactions on drug toxicity. The development of in vivo tools to study OATP1A/1B functions has greatly advanced our mechanistic understanding of their functional role in drug pharmacokinetics, and their implications for therapeutic efficacy and toxic side effects of anticancer and other drug treatments. © 2016 Elsevier Ltden_US
dc.language.isoEnglishen_US
dc.source.titleDrug Resistance Updatesen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.drup.2016.06.005en_US
dc.subjectDrug dispositionen_US
dc.subjectDrug–drug interactionsen_US
dc.subjectHepatic uptakeen_US
dc.subjectOATP1A/1B transportersen_US
dc.subjectOATP1B1en_US
dc.subjectOATP1B3en_US
dc.titleThe impact of organic anion-transporting polypeptides (OATPs) on disposition and toxicity of antitumor drugs: insights from knockout and humanized miceen_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Genetics
dc.citation.spage72en_US
dc.citation.epage88en_US
dc.citation.volumeNumber27en_US
dc.identifier.doi10.1016/j.drup.2016.06.005en_US
dc.publisherChurchill Livingstoneen_US


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