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Published on: November 8, 2015
Pharmacogenetic influences on mycophenolate therapy
Katherine A Barraclough1, Katie J Lee, Christine E Staatz
1Department of Nephrology, Level 2, ARTS Building, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Qld 4102, Australia. katherine_barraclough@health.qld.gov.au
Abstract:
Mycophenolic acid (MPA) is a cornerstone immunosuppressant therapy in solid organ transplantation. MPA is metabolized by uridine diphosphate glucuronosyltransferase to inactive 7-O-MPA-glucuronide (MPAG). At least three minor metabolites are also formed, including a pharmacologically active acyl-glucuronide. MPA and MPAG are subject to enterohepatic recirculation. Biliary excretion of MPA/MPAG involves several transporters, including organic anion transporting polypeptides and multidrug resistant protein-2 (MRP-2). MPA metabolites are also excreted via the kidney, at least in part by MRP-2. MPA exerts its immunosuppressive effect through the inhibition of inosine-5-monophosphate dehydrogenase. Several SNPs have been identified in the genes encoding for uridine diphosphate glucuronosyltransferase, organic anion transporting polypeptides, MRP-2 and inosine-5-monophosphate dehydrogenase. This article provides an extensive overview of the known effects of these SNPs on the pharmacokinetics and pharmacodynamics of MPA.
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