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• W2015031146 abstract "1. Organic anion transporting polypeptide 1B1 plays a pivotal role in the disposition of many anionic drugs. Significant overlap in substrate specificity between individual OATP isoforms has hampered the identification of the relative importance of individual isoforms for hepatic uptake of xenobiotics.2. The present study focused on the use of siRNA technology to decrease OATP1B1 selectively in human hepatocytes. Following delivery of siRNA by the novel lipid, AtuFECT01, mRNA expression of OATP1B1 was reduced by 94%–98% with no significant toxicity. Off-target effects were also shown to be minimal as evidenced by the expression of common drug metabolizing enzymes, transporters, nuclear receptors and associated co-regulators. Uptake of estrone-3-sulfate (5 nM) by OATP1B1 was reduced by 82%–95%. This methodology was subsequently used to assess the relative contribution of OATP1B1 uptake in human hepatocytes for olmesartan (42%–62%), valsartan (28%–81%), rosuvastatin (64%–72%), pitavastatin (84%–98%) and lopinavir (64%–89%). These data are consistent with previous values obtained using a relative activity factor approach.3. The siRNA approach provides a robust and reproducible method for assessing the relative contribution of OATP1B1 to hepatic uptake of new chemical entities. The technique also has potential utility in facilitating detailed characterization of drug–drug interactions involving hepatic drug transporters." @default.
• W2015031146 created "2016-06-24" @default.
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• W2015031146 date "2013-03-06" @default.
• W2015031146 modified "2023-10-09" @default.
• W2015031146 title "Dissecting the relative contribution of OATP1B1-mediated uptake of xenobiotics into human hepatocytes using siRNA" @default.
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• W2015031146 doi "https://doi.org/10.3109/00498254.2013.776194" @default.
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