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

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.