gut metabolism & efflux transporters

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The first-pass effect is not just about the liver. The interface between the lumen of the small intestine and the lining of the small intestine also plays an important role in drug absorption and bioavailability. The lining of the intestine contains metabolic enzymes much like the ones found in the liver, including some members of the CYP family. These enzymes can break down drugs before they even reach the hepatic portal system. This is called gut metabolism. Efflux transporters, including P-glycoprotein, multidrug resistance proteins, and breast cancer resistance protein, can also actively pump drugs back out into the small intestine lumen against the natural concentration gradient. Both of these factors decrease bioavailability.