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Deciphering the Relative Contribution of CYP3A4 Versus P-Glycoprotein for the Shared Substrate
Ingolf Cascorbi1, Richard B Kim2
1Institute of Experimental and Clinical Pharmacology, University Hospital Schleswig-Holstein, Kiel, Germany.
Abstract:
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.
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