Pharmacokinetics and Pharmacodynamics of Mycophenolate in Patients After Renal Transplantation

  • 26 Jun 2019
  • Academic staff's Published Research - Pharmacy


Thomas Rath and Manfred Küpper

Published in

Book/Renal Transplantation – Updates and Advances, 2012


Mycophenolic-acid (MPA) is a selective, non-competitive inhibitor of Inosine-Monophosphate-Dyhydrogenase (IMPDH) leading to the inhibition of the de-novo synthesis of guanosine-nucleotides. In human lymphocytes inhibition of IMPDH results in altered cellular proliferation with arrest in the S-phase of the cell cycle. Due to the absence of a salvage pathway, proliferating activated t-cells are severely affected by the inhibitory effects of MPA (1-3). For patients after renal transplantation MPA is used either as mycophenolate-mofetil (MMF, Cellcept) or as enteric-coated mycophenolate-Sodium (ECMPS, Myfortic) in daily doses of 2000 mg respectively 1440 mg per day.

Since its introduction in immunosuppressive therapy more than ten years ago, Mycophenolate-Mofetil (MMF) is an established part of immunosuppressive therapy after renal transplantation. Still in the first publication of the landmark Tricontinental trial because of possibly dose-related side effects of the drug (CMV-infection, gastrointestinal

disturbances, and increased cancer risk) the need for individualization depending on clinical course or other factors was mentioned (4).

The usefulness of pharmacokinetic measurements of MMF was shown in early studies stating that the Area-under the curve (AUC) of MMF is predictive of the likelihood of allograft rejection after renal transplantation in patients receiving mycophenolate mofetil (5).

To facilitate therapeutic drug monitoring different limited sampling strategies for adult and pediatric patients after renal transplantation were established (6-13).

The two available preparations of MPA (MMF, EC-MPS) showed equivalent drug exposure measured by MPA-AUC when applied to the patients in equimolar doses. Therefore, both preparations are seen as equipotent (14-16).

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