Bioequivalence of enteric-coated mycophenolate sodium and mycophenolate mofetil: a meta-analysis of three studies in stable renal transplant recipients.

BACKGROUND

Mycophenolic acid (MPA) is an inhibitor of lymphocyte proliferation and is well established as an immunosuppressive agent in solid organ transplantation. The initial formulation of the drug was a prodrug formulation, mycophenolate mofetil (MMF, Cellcept), which is well absorbed and rapidly converted to mycophenolate in plasma. However, the use of MMF is associated with adverse gastrointestinal events, which can lead to withdrawal of therapy. In an effort to reduce the gastrointestinal effects of MMF, an enteric-coated formulation of the drug was developed, based on the sodium salt of MPA (EC-MPS, Myfortic).

METHODS

Although bioequivalence has been demonstrated in an individual study in maintenance kidney transplant patients, this manuscript documents bioequivalence in a much larger data set of 82 patients by a meta-analysis of data from clinical trials.

RESULTS

The results confirm the bioequivalence of EC-MPS and MMF for both mycophenolate and metabolite exposure, and for maximum plasma mycophenolate concentrations, across three studies. The 90% confidence interval of the ratio of EC-MPS to MMF for mycophenolate plasma AUC in the 82 patients was 101.1 to 114.5% and for Cmax was 83.0% to 112.7%.

CONCLUSION

These findings provide reassurance to transplant professionals and patients that, when choosing between EC-MPS and MMF, they are choosing between formulations that give equivalent mycophenolate exposure.