eISSN 2329-0358


Drug transporters for immunosuppressive agents

I.A.M. MacPhee

Ann Transplant 2008; 13(1): 15-15

ID: 880169


Several drug transporters influence the pharmacokinetics and pharmacodynamics of the immunosuppressive drugs in widespread use. P-glycoprotein (P-gp), the product of the ABCB1 gene (previously known as MDR-1) is a drug efflux pump that extrudes hydrophobic molecules from cells. The calcineurin inhibitors (ciclosporin and tacrolimus), the mTOR inhibitors (sirolimus and everolimus) and corticosteroids are all transported by P-gp. The genotype at several linked single nucleotide polymorphisms in the ABCB1 may predict the level of P-gp expression but this is controversial. P-gp is one component of the active barrier to drug absorption and differences in intestinal P-gp expression have been shown to influence the absorption of tacrolimus. Data from clinical studies and in vitro experiments suggest that a high level of P-gp expression on T-lymphocytes reduces the efficacy of a number of drugs including ciclosporin and the anti-retrovirals. Induction or inhibition of P-gp expression is probably responsible for a number of the drug interactions with immunosuppressive drugs, although the fact that most of these agents also induce and inhibit cytochrome P450 renders this issue complex. The glucuronide metabolites of mycophenolic acid are secreted into bile by the drug efflux pump ABCC2 (formerly known as MRP2) leading to a second peak of absorption due to enterohepatic recirculation. Ciclosporin inhibits ABCC2 with loss of the enterohepatic recirculation and reduced exposure to mycophenolic acid. Although the immunosuppressive drugs are not transported by the organic anion transporting polypeptide (OATP), inhibition of this pump may be responsible for the increased exposure to statins in ciclosporin-treated patients.

Keywords: immunosuppressive drugs, P-Glycoprotein, flu shot