The oral bioavailability of cyclosporine, a substrate of both CYP3A4 and P-glycoprotein, is subject to large inter-individual variability, which requires frequent monitoring of plasma concentrations. In 1997, the study by Lown et al. showed that-in addition to hepatic CYP3A4-the expression of P-gp in the intestine significantly influences the pharmacokinetics of cyclosporine in kidney transplant patients. The results contributed considerably to a better understanding of the function of the intestinal P-glycoprotein for drug clearance.