Ácido micofenólico en trasplante renal ¿El problema es la selección de la dosis o su alta variabilidad farmacocinética?

Abstract

Introduction. Mycophenolic acid, in combination with tacrolimus, is the cornerstone of the immunosuppressive therapy in transplants. Nevertheless, its use is controversial because it is associated with adverse events, high variability in plasma concentrations, and because monitoring it in plasma levels is still debatable. Case presentation. A female sixteen-year-old patient with kidney transplant and with maintenance immunosup-pressive therapy. She had been treated with mycophenolate mofetil, tacrolimus, and prednisone according to her size and weight, but she presented recurrent gastrointestinal disorders associated with the administration of mycophenolate mofetil and with overexposure to the drug. Pharmacokinetic monitoring of mycophenolate mofetil was performed and the findings showed high levels of the drug (double concentration); then the dose was reduced. Nevertheless, after two attempts to adjust the levels (and the corresponding monitoring), the goal levels were not achieved; she passed from overexposure to underexposure; there was no relationship among doses adjustments. Based on the risk of graft rejection due to plasma concentration variability, azathioprine was used as an antimetabolite drug instead of mycophenolic acid and the outcomes were good. Conclusions. The pharmacokinetic monitoring was useful to identify overexposure to mycophenolic acid, but it was not possible to properly adjust the dose regimen due to the pharmacokinetic variability, even though the literature claims that mycophenolic acid shows linear pharmacokinetics.