Therapeutic monitoring of immunosuppressant drugs. Where are we?

Abstract

The emergence of specific immunosuppressive drugs (cyclosporine, tacrolimus, mycophenolate mofetil and sirolimus) during the last two decades has contributed dramatically to the success of organ transplantation. However, optimum balance between therapeutic efficacy and the occurrence of side effects has been a real challenge for physicians, mainly due to inter- and intra-patient variability arising from pharmacokinetic, pharmacogenetic and pharmacodynamic individual properties. Therapeutic drug monitoring, defined as the measurement and interpretation of concentrations of these drugs in biological fluids, with as a final objective the prediction of organ responses, became an integral part of transplant protocols. New analytical techniques became available with different performances in terms of specificity and sensitivity. In addition, there has been progress in understanding the mechanisms of action of these drugs that have implications for the development of better monitoring strategies and for their coprescription. The purpose of this review is to examine the current strategies in use for the therapeutic drug monitoring of immunosuppressant drugs and to discuss some of the factors that impinge on the monitoring of these drugs.