title: Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients.
abstract: This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6-12 yr (n = 18), and 13-17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 microg/mL (2.48-8.78), 4.54 microg/mL (1.79-18.7), and 4.94 microg/mL (0.05-10.6) in the less than or equal to five yr (n = 15), 6-12 yr (n = 17), and 13-17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg x h/mL (1585-3778), 2757 mg x h/mL (1873-3494) and 3297 mg x h/mL (1705-6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.
authors.affiliation: Department of Surgery, Indiana University, Indianapolis, IN 46202, USA. mpescov@iupui.edu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Pescovitz
authors.forename: Stuart
authors.initials: S
authors.lastname: Knechtle
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alexander
authors.forename: Paul
authors.initials: P
authors.lastname: Colombani
authors.forename: Tom
authors.initials: T
authors.lastname: Nevins
authors.forename: Keith
authors.initials: K
authors.lastname: Nieforth
authors.forename: M René
authors.initials: MR
authors.lastname: Bouw
mesh_terms: D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage; D000077561:Daclizumab; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007223:Infant; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus