title: Pharmacokinetic and pharmacodynamic studies of one or two doses of daclizumab in renal transplantation.
abstract: In phase III trials daclizumab was used in a five-dose regimen of 1 mg/kg at 2-weekly intervals, resulting in saturation of IL-2Ralpha on circulating lymphocytes for up to 120 days after renal transplantation. The purpose of this study was to evaluate daclizumab blood concentrations and the saturation of the IL-2Ralpha on the circulating lymphocytes with a limited dosing regimen of daclizumab. Twelve patients undergoing primary cadaver or living donor transplantation were randomized to either receive one dose (2 mg/kg) or two doses (2nd dose, 1 mg/kg) of daclizumab in addition to maintenance immunosuppression therapy consisting of either tacrolimus or cyclosporine, mycophenolate mofetil and prednisone. Patients were followed for 6 months after the transplantation. Pharmacokinetic and pharmacodynamic studies were performed up to 20 weeks after the transplantation. In patients treated with a single dose of daclizumab, the blood concentrations of daclizumab declined to 1 micro g/mL at 43 +/- 7 days after the transplantation. In patients treated with two doses of daclizumab, the blood concentrations of daclizumab declined to 1 micro g/mL at 45 +/- 13 days after the second dose for a total of 59 +/- 13 days after the transplantation. Daclizumab levels of 1 micro g/mL or greater were associated with saturation of the IL-2Ralpha on the circulating lymphocytes. In the new era of effective maintenance immunosuppression, a limited dosing regimen of daclizumab may be desired, practical and economical.
authors.affiliation: University of California, San Francisco, CA, USA. vincentif@surgery.ucsf.edu
authors.forename: Flavio
authors.initials: F
authors.lastname: Vincenti
authors.forename: Daniel
authors.initials: D
authors.lastname: Pace
authors.forename: Jytte
authors.initials: J
authors.lastname: Birnbaum
authors.forename: Marianne
authors.initials: M
authors.lastname: Lantz
mesh_terms: D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D053645:Interleukin-2 Receptor alpha Subunit; D016030:Kidney Transplantation; D018123:Receptors, Interleukin / Q000378:metabolism; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C508017:IL2RA protein, human; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D000077561:Daclizumab