Pharmacogenetic Influences on Mycophenolate Therapy

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.

KEYWORDS::

• mycophenolate
• mycophenolic acid
• pharmacodynamics
• pharmacogenetics
• pharmacogenomics
• pharmacokinetics
• polymorphism

Financial & competing interests disclosure

Katherine Barraclough is currently supported by a National Health and Medical Research Council Medical/Dental Post-graduate Research Scholarship. Christine Staatz is currently supported by a Lions Medical Research Fellowship. This research is supported by a National Health and Medical Research Council Project Grant, number 511109. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Katherine Barraclough is currently supported by a National Health and Medical Research Council Medical/Dental Post-graduate Research Scholarship. Christine Staatz is currently supported by a Lions Medical Research Fellowship. This research is supported by a National Health and Medical Research Council Project Grant, number 511109. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.