Deciphering the Relative Contribution of CYP3A4 Versus P‐Glycoprotein for the Shared Substrate Cyclosporine—Commentary on Lown et al .

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.