Why and How to Perform Therapeutic Drug Monitoring for Mycophenolate Mofetil

The introduction of the immunosuppressive agent mycophenolate mofetil as a standard-dose drug has resulted in a reduced risk of rejection after renal transplantation and improved graft survival compared to azathioprine. The favorable balance between efficacy and safety has made mycophenolate mofetil a cornerstone immunosuppressive drug, and the vast majority of newly transplanted patients are now started on mycophenolate mofetil therapy. Despite the obvious success of mycophenolate mofetil as a standard-dose drug, there is reason to believe that the “one size fits all” approach is not optimal. Recent studies have shown that the pharmacokinetics of mycophenolic acid are influenced by patient characteristics such as gender, time after transplantation, serum albumin concentration, renal function, co-medication, and pharmacogenetic factors. As a result, with standard-dose therapy there is wide between-patient variability in exposure of mycophenolic acid. This variability is of clinical relevance because it has repeatedly been shown that exposure to the active metabolite mycophenolic acid is correlated with the risk of developing acute rejection. Especially with the increasing popularity of immunosuppressive regimens in which the concomitant immunosuppression is reduced or eliminated, ensuring an appropriate level of immunosuppression afforded by mycophenolic acid is of utmost importance. By introducing therapeutic drug monitoring, mycophenolic acid exposure can be targeted to the widely accepted therapeutic window (mycophenolic acid AUC0-12 between 30 and 60 mg·h/l). Three prospective randomized studies comparing concentration-controlled mycophenolate mofetil therapy to a fixed-dose regimen will further clarify the role of therapeutic drug monitoring in increasing the therapeutic potential of mycophenolate mofetil. (Trends in Transplant 2007;1:24-34) Corresponding author: Teun van Gelder, [email protected]