Is CD25 blockade optimal in kidney transplant patients treated with basiliximab? A target-mediated drug disposition model

Br J Clin Pharmacol. 2022 Jul;88(7):3500-3505. doi: 10.1111/bcp.15235. Epub 2022 Feb 1.

Abstract

Aims: Basiliximab, an anti-CD25 chimeric monoclonal antibody, is approved in prevention of acute kidney transplant rejection. This study aims at investigating target-mediated pharmacokinetics of basiliximab.

Methods: Data from the IDEALE study, where 16 kidney transplant patients were treated with 2 40- or 80-mg basiliximab injections, were reanalysed. Basiliximab pharmacokinetics was described using a population 2-compartment target-mediated drug disposition model with the quasi-steady-state approximation.

Results: Volume of distribution was significantly higher in males (P = .029). Estimated baseline target antigen (CD25) level was lower is patients cotreated with cyclosporine (P = .026).

Conclusion: This analysis allows the first description of the target-mediated nonlinear elimination of basiliximab. Our results suggest that cyclosporine cotreatment is associated with decreased target level and that an optimized dosing regimen may improve basiliximab effects.

Keywords: CD25; basiliximab; cyclosporine; kidney transplantation; monoclonal antibody; pharmacokinetics; target-mediated drug disposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Basiliximab
  • Cyclosporine
  • Drug Therapy, Combination
  • Graft Rejection / prevention & control
  • Humans
  • Immunosuppressive Agents
  • Kidney Transplantation*
  • Male
  • Recombinant Fusion Proteins

Substances

  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • Recombinant Fusion Proteins
  • Cyclosporine
  • Basiliximab