Pharmacokinetic and Pharmacodynamic Studies of One or Two Doses of Daclizumab in Renal Transplantation

Authors


  • Supported by Roche Laboratories Inc., Nutley, NJ.

*Corresponding author: Flavio Vincenti, MD, vincentif@surgery.ucsf.edu

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-2Rα 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-2Rα 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 µg/mL at 43 ± 7 days after the transplantation. In patients treated with two doses of daclizumab, the blood concentrations of daclizumab declined to 1 µg/mL at 45 ± 13 days after the second dose for a total of 59 ± 13 days after the transplantation. Daclizumab levels of 1 µg/mL or greater were associated with saturation of the IL-2Rα on the circulating lymphocytes.

In the new era of effective maintenance immunosuppression, a limited dosing regimen of daclizumab may be desired, practical and economical.

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