The effect of rifampin treatment on intestinal expression of human MRP transporters

The importance of the ATP-dependent transporter P-glycoprotein, which is ex pressed in the brush border membrane of enterocytes and In other tissues wi th excretory function, for overall drug disposition Is well recognized. For example, induction of intestinal P-glycoprotein by rifampin appears to be the underlying mechanism of decreased plasma concentrations of P-glycoprote in substrates such as digoxin with concomitant rifampin therapy. The contri bution of transporter proteins other than P-glycoprotein to drug interactio ns in humans has not been elucidated. Therefore, we tested in this study th e hypothesis whether the conjugate export pump MRP2 (cMOAT), which is anoth er member of the ABC transporter family, is inducible by rifampin in humans . Duodenal biopsies were obtained from 16 healthy subjects before and after nine days of oral treatment with 600 mg rifampin/day. MRP2 mRNA and protei n were determined by reverse transcription-polymerase chain reaction and im munohistochemistry. Rifampin induced duodenal MRP2 mRNA in 14 out of 16 ind ividuals, Moreover, MRP2 protein, which was expressed In the apical membran e of enterocytes, was significantly induced by rifampin in 10 out of 16 sub jects. In summary, rifampin induces MRP2 mRNA and protein in human duodenum , Increased elimination of MRP2 substrates leg, drug conjugates) into the l umen of the gastrointestinal tract during treatment with rifampin could be a new mechanism of drug interactions.