Clinical pharmacokinetic and pharmacodynamic monitoring for mycophenolate mofetil

The use of mycophenolate mofetil (MMF), in combination with cyclosporine (CsA) or tacrolimus (FK) and corticosteroids, has been shown to improve clinical outcomes through significant reduction in the incidence of acute rejection in solid organ transplant patients. A fixed oral dosing regimen of 1 or 1.5 g MMF twice daily received Food and Drug Administration approval in 1995 with no recommendations for concentration monitoring at that time. Subsequent evidence has generated substantial debate on the need of clinical monitoring for MMF. This article summarizes the rationale, evidence, and approaches of clinical monitoring, for MMF. Mycophenolic acid (MPA), the active moiety of MMF, noncompetitively inhibits the enzyme inosine monophosphate dehydrogenase (IMPDH), which is the target enzyme for MPA. Pharmacokinetic monitoring, by use of MPA predose or MPA area under the concentration-time curve (AUC) values, and pharmacodynamic monitoring by analysis of inhibition of IMPDH have been evaluated in organ transplant patients. The possibility of drug interactions between other immunosuppressive agents has also received attention recently. The clinical implications of drug interactions are discussed in this article.