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• W2158979706 abstract "Organic anion-transporting polypeptides (OATPs) are multispecific transporters mediating the uptake of endogenous compounds and xenobiotics in tissues that are important for drug absorption and elimination, including the intestine and liver. Silymarin is a popular herbal supplement often used by patients with chronic liver disease; higher oral doses than those customarily used (140 mg three times/day) are being evaluated clinically. The present study examined the effect of silymarin flavonolignans on OATP1B1-, OATP1B3-, and OATP2B1-mediated transport in cell lines stably expressing these transporters and in human hepatocytes. In overexpressing cell lines, OATP1B1- and OATP1B3-mediated estradiol-17<i>β</i>-glucuronide uptake and OATP2B1-mediated estrone-3-sulfate uptake were inhibited by most of the silymarin flavonolignans investigated. OATP1B1-, OATP1B3-, and OATP2B1-mediated substrate transport was inhibited efficiently by silymarin (IC₅₀ values of 1.3, 2.2 and 0.3 <i>µ</i>M, respectively), silybin A (IC₅₀ values of 9.7, 2.7 and 4.5 <i>µ</i>M, respectively), silybin B (IC₅₀ values of 8.5, 5.0 and 0.8 <i>µ</i>M, respectively), and silychristin (IC₅₀ values of 9.0, 36.4, and 3.6 <i>µ</i>M, respectively). Furthermore, silymarin, silybin A, and silybin B (100 <i>µ</i>M) significantly inhibited OATP-mediated estradiol-17<i>β</i>-glucuronide and rosuvastatin uptake into human hepatocytes. Calculation of the maximal unbound portal vein concentrations/IC₅₀ values indicated a low risk for silymarin-drug interactions in hepatic uptake with a customary silymarin dose. The extent of silymarin-drug interactions depends on OATP isoform specificity and concentrations of flavonolignans at the site of drug transport. Higher than customary doses of silymarin, or formulations with improved bioavailability, may increase the risk of flavonolignan interactions with OATP substrates in patients." @default.
• W2158979706 created "2016-06-24" @default.
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• W2158979706 date "2013-02-11" @default.
• W2158979706 modified "2023-10-15" @default.
• W2158979706 title "Interaction of Silymarin Flavonolignans with Organic Anion-Transporting Polypeptides" @default.
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• W2158979706 doi "https://doi.org/10.1124/dmd.112.048272" @default.
• W2158979706 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3629808" @default.
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