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doi:10.1136/gutjnl-2013-305965 Cremonini F, Nicandro JP, Atkinson V, Shringarpure R, Chuang E, Lembo A

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Even before reaching the liver, part of the dose may already be metabolized by intestinal enzymes such as CYP3A4 and UGTs, or pumped back into the intestinal lumen by efflux transporters like P-glycoprotein (ABCB1)