Disposition and immunodynamics of basiliximab in liver allograft recipients.
A randomized, open-label prospective study was conducted with recipients of primary cadaveric liver allografts to characterize the disposition and immunodynamics of basiliximab, an interleukin-2 receptor, alpha-chain chimeric monoclonal antibody for immunoprophylaxis of acute rejection. Patients received a total intravenous dose of 40 mg basiliximab in addition to baseline dual immunosuppression consisting of cyclosporine (INN, ciclosporin) and steroids. The central distribution volume was 5.6 +/- 1.7 L with a steady-state volume of 7.5 +/- 2.5 L. It was cleared slowly with a total body clearance of 75 +/- 24 ml/hr and an elimination half-life of 4.1 +/- 2.1 days. Basiliximab was measurable in drained ascites fluid, and clearance by this route was an average of 20% of total clearance. Total body clearance correlated positively with volume of postoperative blood loss (r = 0.5253, p = 0.0101), suggesting that bleeding may represent an additional route of drug removal. A threshold relation was observed between serum concentration of basiliximab and CD25 expression on T lymphocytes whereby complete saturation of interleukin-2 receptor alpha-chain was maintained as long as serum concentrations exceeded 0.1 microgram/ml. The duration of receptor saturation was 23 +/- 7 days after transplantation (range, 13 to 41 days).
Novartis Pharma AG, Basel, Switzerland.
J
J
Kovarik
T
T
Breidenbach
C
C
Gerbeau
A
A
Korn
A G
AG
Schmidt
B
B
Nashan
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077552:Basiliximab; D016572:Cyclosporine / Q000494:pharmacology; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D016031:Liver Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000276:immunology; D011993:Recombinant Fusion Proteins; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab