Interleukin-2 Receptor Antagonist Therapy Leads to Increased Tacrolimus Levels After Kidney Transplantation
Year of Publication
Lin, S; Henning, A; Akhlaghi, F; Reisfield, R; Vergara-Silva, A; First, MR
Ther Drug Monit
BACKGROUND:: Tacrolimus is a known substrate for cytochrome P450 (CYP) enzyme. CYP enzyme activity can be modulated via activation of IL-2 receptors (IL-2R) expressed on hepatocytes and intestinal cells. IL-2R antagonists (IL-2RA) may promote preferential binding of circulating IL-2 to IL-2Rs on these cells by blocking IL-2Rs on activated T-cells. This down-regulates CYP enzymes, leading to increased CNI levels. This analysis evaluates the significance of this drug-drug interaction in kidney transplant recipients. METHODS:: Data was utilized from a previous 5-year randomized, controlled study comparing outcomes associated with maintenance immunosuppression using 2 corticosteroid regimens: long-term therapy versus early withdrawal. Patients received either IL-2RAs or anti-thymocyte globulin (rATG) for induction. Serial tacrolimus trough levels and doses were compared between induction agents within each corticosteroid arm. Rejection rates, patient/graft survival and tacrolimus adverse effects were also evaluated. RESULTS:: In the first week, IL-2RA-treated patients achieved significantly higher trough levels and required lower doses (mg/kg) to achieve target levels than rATG-treated patients. No significant differences in rejection rates, patient/graft survival or rate of adverse effects were observed through 1 year.