01 January 2008
Drug transporters for immunosuppressive agents
I.A.M. MacPheeAnn Transplant 2008; 13(1): 15-15 :: ID: 880169
Abstract
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
In Press
08 Mar 2024 : Original article
Association of Coronary Calcium Score on Cardiac PET During Pre-Kidney Transplant Assessment with Persisten...Ann Transplant In Press; DOI: 10.12659/AOT.943532
14 Mar 2024 : Original article
Impact of Blood Products Transfusion on Patients in the Immediate Post-Lung Transplant Period: A Cohort StudyAnn Transplant In Press; DOI: 10.12659/AOT.943652
14 Mar 2024 : Case report
Treatment of Cavernous Transformation of Portal Vein Caused by Hepatic Cystic Echinococcosis Using Ex Vivo ...Ann Transplant In Press; DOI: 10.12659/AOT.942358
15 Mar 2024 : Review article
Approaches and Challenges in the Current Management of Cytomegalovirus in Transplant Recipients: Highlighti...Ann Transplant In Press; DOI: 10.12659/AOT.941185
Most Viewed Current Articles
05 Apr 2022 : Original article
Impact of Statins on Hepatocellular Carcinoma Recurrence After Living-Donor Liver TransplantationDOI :10.12659/AOT.935604
Ann Transplant 2022; 27:e935604
12 Jan 2022 : Original article
Risk Factors for Developing BK Virus-Associated Nephropathy: A Single-Center Retrospective Cohort Study of ...DOI :10.12659/AOT.934738
Ann Transplant 2022; 27:e934738
22 Nov 2022 : Original article
Long-Term Effects of Everolimus-Facilitated Tacrolimus Reduction in Living-Donor Liver Transplant Recipient...DOI :10.12659/AOT.937988
Ann Transplant 2022; 27:e937988
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860