Disposition of basiliximab, an interleukin-2 receptor monoclonal antibody, in recipients of mismatched cadaver renal allografts.
BACKGROUND
Basiliximab is an interleukin-2 receptor (IL-2R; 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 microg/ml are sufficient to saturate IL-2R 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.
Kovarik
J
J
Novartis Pharma Inc., Basel, Switzerland.
Wolf
P
P
Cisterne
J M
JM
Mourad
G
G
Lebranchu
Y
Y
Lang
P
P
Bourbigot
B
B
Cantarovich
D
D
Girault
D
D
Gerbeau
C
C
Schmidt
A G
AG
Soulillou
J P
JP
D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002102:Cadaver; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006085:Graft Survival / Q000187:drug effects; D006648:Histocompatibility; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D011993:Recombinant Fusion Proteins
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins