Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts

Background. Basiliximab is an interleukin-a receptor (IL-SR; CD25) chimeric monoclonal antibody for immunoprophylaxis against acute rejection in renal transplantation. Its pharmacokinetics were characterized in a multicenter open-label, prospective dose-escalation study to identify a single-dose regimen providing IL-2R-saturating serum concentrations in the critical first posttransplant month, Methods, Thirty-two recipients of primary, mismatched cadaver kidneys were enrolled: 20 men and 12 women, who were 47+/-11 years old and weighed 65+/-12 kg, The immunosuppression regimen consisted of steroids and azathioprine from day 0 and cyclosporine from day 10, Basiliximab was infused over 30 min as a single dose preoperatively, Results, Thirty patients were evaluable for basiliximab pharmacokinetics: 24 received 40 mg and 6 received 60 mg, Basiliximab was well tolerated without evidence of cytokine-release syndrome, hypersensitivity reactions, or anti-idiotype antibody response, Peak concentration and area under the concentration curve increased proportionally with dose, Postinfusion concentrations declined in a biphasic manner with a terminal half-life of 6,5+/-2,1 days, Weak, widely dispersed correlations were noted between body weight versus distribution volume (r=0,29) and versus clearance (r=0,45), suggesting no clinical relevance for weight-adjusted dosing, There were no apparent gender-related differences in basiliximab disposition, Previous phase II data indicated that serum concentrations in excess of 0.2 mu g/ml are sufficient to saturate IL-SR epitopes on circulating T lymphocytes. Concentrations were above this threshold for 26+/-8 days (range 16 to 46) at the 40-mg dose level and for 32+/-11 days (range 22 to 51) at the 60-mg dose level, Conclusions, Total basiliximab doses of 40-60 mg were well tolerated, nonimmunogenic, and estimated to provide immunoprophylaxis to cover the first posttransplant month.