Intestinal drug absorption and bioavailability: beyond involvement of single transport function

Abstract

This review discusses the clin. significance of the carrier-mediated efflux on intestinal absorption and first-pass gut wall metab. of drugs. The human intestinal epithelium expresses efflux proteins that may limit the absorption of xenobiotics and secrete intracellularly formed metabolite(s), including conjugates, back into the intestinal lumen. The multi-drug resistant transporter gene MDR1, which codes for P-glycoprotein (P-gp), is the most extensively studied transporter gene. However, there are other multidrug transporters involved, such as multidrug-resistant protein family (MRP1-MRP9 or ABCC1-ABCC9) and breast-cancer-resistant protein (BRCP1 or ABCG2). These ABC transporters are also expressed in numerous tissues such as the liver, kidney, testes, placenta, and blood-brain barrier and are expected to affect the disposition of drugs and their metabolites. [on SciFinder (R)]