Drug transporters possess the role of detoxification mediating membrane transport of drugs, toxins and waste products. Drug transporters are mainly categorized to 4 groups based on their driving force such as facilitated diffusion, primary active transporter, cotransporter and antiporter. Among them, ATP-driven efflux pump, P-glycoprotein (multidrug resistance-1) recognizes tacrolimus, cyclosporine, steroids, sirolimus and everolimus. In addition, the intestinal Pglycoprotein was well acknowledged as an absorptive barrier for its substrates. The bioavailability of orally administered tascrolimus was limited in the absorptive barrier at the intestinal epithelial cells. The blood concentration/oral dosage of tacrolimus was inversely correlated with the expression level of MDR1 mRNA in the intestinal epithelial cells of recipients. Several single nucleotide polymorphisms (SNP) were examined in the pharmacokinetics of tacrolimus and cyclosporine. However, there was no statistically significant difference in the tacrolimus pharmacokinetics based on MDR1 SNPs. On the other hand, biliary secretion of mycophenolate glucuronide is mediated by the multidrug resistance associated protein-2 (MRP2). Its biliary secretion is decreased in the presence of concomitant administration of cyclosporine. In addition, mycophenolate glucuronide rather than mycophenolate was recognized as the substrate for hOAT3. These results indicate that drug transporters play important role in posttransplant immunosuppressive therapy.
