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.