INTRODUCTION: Therapeutic monitoring of immunosuppressants cyclosporine A (CsA) and tacrolimus (FK506) is indispensable to maintain stable levels of these drugs, avoiding graft rejection in the transplanted patient in the case of low dosage, or toxicity in high dosage, and allowing monitoring of individual treatment. BACKGROUND: In the 80's, the introduction of the potent immunosuppressive drugs CsA and FK506 reduced the incidence of rejection episodes after solid organ transplantation. MECHANISM OF ACTION: CsA and FK506 have distinct chemical structures but similar mechanisms of action, inhibiting the transcription of the first signal for T-lymphocyte activation. TOXICITY: The major side effects associated with CsA and FK506 therapies are nephrotoxicity and neurological disturbances. However, clinical studies demonstrate that FK506 is a potent alternative to CsA due to its lower nephrotoxicity and reversible neurotoxicity when the dosage is decreased. ANALYTICAL METHODOLOGY: For routine monitoring of CsA, the high-performance liquid chromatography with ultraviolet detection (HPLC-UV) was replaced by the radioimmunoassay (RIA) and monoclonal antibody-based fluorescence polarization immunoassay (mFPIA). For the assessment of FK506, it is consensus that highly specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) is the reference method, although the microparticle enzyme immunoassay (MEIA) and the enzyme-linked immunosorbent assay (ELISA) are currently used for routine monitoring. CONCLUSION: There is a tendency to substitute CsA by FK506 at immunosuppressive regimens, but this is not a consensus yet. The analytical methodology for CsA analysis is well established in the clinical laboratory, but further studies are needed to define the best methodologies for routine FK506 analysis.
Immunosuppressant; Therapeutic monitoring; Cyclosporine A; Tacrolimus; Toxicity