Therapeutic drug monitoring of mycophenolic acid

Mycophenolate mofetil (MMF) is a prodrug of the 2-morpholinoethylester of mycophenolic acid (MPA). MPA inhibits the key enzyme of the de novo pathway, inosine monophosphate dehydrogenase (IMPDH). This factor is responsible for the immunosuppression. MPA is not only used to prevent transplant rejection, but also to treat autoimmune diseases. Therapeutic drug monitoring (TDM) for MPA has always been questioned, because studies had not offered a definitive outcome whether it is useful or not to implement TDM. In this retrospective study we analysed MPA trough levels of 50 patients. These patients had either autoimmune disease (lupus nephritis, IgA nephritis, chronic glomerular disease or rapid progressive glomerulonephritis), or were transplant recipients (kidney, liver, heart) or it was given to prevent acute graft versus host disease. Our main objective was to determine the usefulness and clinical relevance of TDM for MPA trough level concentrations. To verify this, we compared mean MPA trough level concentrations and set them in correlation with clinical factors, such as gender, age, diagnosis, renal parameters, co-medication and side effects. MPA trough levels were higher in patients with autoimmune diseases than in transplant recipients. Gender, diagnosis, concomitant therapy with CyclosporinA, pantoprazole and blood pressure effects MPA trough levels and MPA trough levels in return effects the outcome, which correlates with renal retention parameters. Furthermore, few actions were taken regarding the MPA trough level concentrations. We do not know whether it was lack of compliance, discipline or some other reasons. No correlation was found between side effects (gastrointestinal discomfort, infections or leukopenia) and MPA trough level concentrations. The results of our retrospective study do not support the implementation of TDM. Renal retention parameters, CyclosporinA dose should be considered to predict MPA exposure. The vast intra- and inter-patient variability in the pharmacodynamics and pharmacokinetics of MPA mentioned in many studies needs to be studied in more detail to deliver a clear answer for the TDM for MPA. Based on current findings, TDM for MPA is still a big question mark; more studies are eagerly awaited.