title: Interleukin-2 receptor antagonist therapy leads to increased tacrolimus levels after kidney transplantation.
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.
authors.affiliation: *Department of Pharmacy, University of Colorado Hospital, Aurora; †The EMMES Corporation, Rockville, Maryland; ‡Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston; §Astellas Scientific and Medical Affairs, Inc, Northbrook, Illinois; ¶Ziopharm Oncology, Boston, Massachusetts; and ‖Astellas Pharma Global Development, Inc, Northbrook, Illinois.
authors.forename: Sonia
authors.initials: S
authors.lastname: Lin
authors.forename: Alice K
authors.initials: AK
authors.lastname: Henning
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Akhlaghi
authors.forename: Robin
authors.initials: R
authors.lastname: Reisfield
authors.forename: Andrea
authors.initials: A
authors.lastname: Vergara-Silva
authors.forename: M Roy
authors.initials: MR
authors.lastname: First
mesh_terms: D000328:Adult; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D012189:Retrospective Studies; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000961:Antilymphocyte Serum; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D016559:Tacrolimus