Interleukin-2 Receptor Antagonist Therapy Leads to Increased Tacrolimus Levels After Kidney Transplantation. Issue 2 (April 2015)

• Record Type: Journal Article
• Authors: Lin, Sonia; Henning, Alice K.; Akhlaghi, Fatemeh; Reisfield, Robin; Vergara-Silva, Andrea; First, M. Roy
• Is Part Of: Therapeutic drug monitoring. Volume 37:Issue 2(2015:Apr.)
• Publication Date: 2015-04
• Subjects: calcineurin inhibitors -- interleukin-2 receptor antagonists -- pharmacokinetics -- corticosteroids -- drug–drug interaction; Pharmacokinetics -- Periodicals; Patient monitoring -- Periodicals; Drugs -- Analysis -- Periodicals; Body fluids -- Analysis -- Periodicals; Drug Therapy -- Periodicals; Monitoring, Physiologic -- Periodicals; Pharmacology -- Periodicals; 615.7
• DOI: 10.1097/FTD.0000000000000125
• Languages: English
• ISSNs: 0163-4356

Abstract

Abstract : Background: Tacrolimus (TAC) is a known substrate for cytochrome P450 (CYP) enzyme. CYP enzyme activity can be modulated by 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 downregulates CYP enzymes, leading to increased calcineurin inhibitor levels. This analysis evaluates the significance of this drug–drug interaction in kidney transplant recipients. Methods: Data were used 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 rabbit anti-thymocyte globulin (rATG) for induction. Serial TAC trough levels and doses were compared between induction agents within each corticosteroid arm. Rejection rates, patient/graft survival, and TAC adverse effects were also evaluated. Results: In the first week, IL-2RA–treated patients achieved significantly higher trough levels and required lower doses (in milligram per kilogram) 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.