Pharmacogenetic influences on mycophenolate therapy

Author:

Barraclough Katherine A1,Lee Katie J2,Staatz Christine E2

Affiliation:

1. Department of Nephrology, Level 2, ARTS Building, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, Qld 4102, Australia.

2. School of Pharmacy, University of Queensland, Brisbane, Australia

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.

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

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