Therapeutic Monitoring of Mycophenolic Acid: Is There Clinical Utility?

Mycophenolate mofetil (MMF) is the ester prodrug of the active immunosuppressant mycophenolic acid (MPA), an uncompetitive, selective and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH). The pharmacokinetic profile of MPA is complex. MPA, as opposed to most other agents utilized in transplantation, undergoes glucoronidation as the first step in its metabolism. In addition, it undergoes extensive enterohepatic recirculation and its clearance is highly dependent on protein binding (restrictive clearance). Thus, interpretation of any monitoring strategy can be confounded by these complex processes. As an example, MPA does not have dose linearity over the first several months of administration. Therefore, at any given dose, exposure is lower in the very early posttransplant period than at later time points. These lower MPA concentrations in the immediate posttransplant period may be the result of renal dysfunction and uremia which results in decreased binding of MPA to serum albumin and increased clearance of free MPA. In addition, it is unclear if early steroid usage and changes in enterohepatic recirculation may also contribute to this ‘adaptation’ over time.