Chemical formula: C₆₃₇₈H₉₈₄₄N₁₆₉₈O₁₉₉₇S₄₈
Basiliximab is a murine/human chimeric monoclonal antibody (IgG1κ) that is directed against the interleukin-2 receptor α-chain (CD25 antigen), which is expressed on the surface of T-lymphocytes in response to antigenic challenge. Basiliximab specifically binds with high affinity (KD-value 0.1 nM) to the CD25 antigen on activated T-lymphocytes expressing the high affinity interleukin-2 receptor (IL-2R) and thereby prevents binding of interleukin-2, a critical signal for T-cell proliferation in the cellular immune response involved in allograft rejection. Complete and consistent blocking of the interleukin-2 receptor is maintained as long as serum basiliximab levels exceed 0.2 g/ml (usually up to 4–6 weeks after administration). As concentrations fall below this level, expression of the CD25 antigen returns to pretherapy values within 1–2 weeks. Basiliximab does not cause myelosuppression.
Single-dose and multiple-dose pharmacokinetic studies have been conducted in adult patients undergoing kidney transplantation. Cumulative doses ranged from 20 mg up to 60 mg. Peak serum concentration following intravenous infusion of 20 mg over 30 minutes is 7.15.1 mg/l. There is a proportional increase in Cmax and AUC from 20 mg to 60 mg, the range of single-dose administrations tested. The volume of distribution at steady state was 8.6±4.1 l. The extent and degree of distribution to various body compartments have not been fully studied. In vitro studies using human tissues indicate that basiliximab binds only to activated lymphocytes and macrophages/monocytes. The terminal half-life was 7.2±3.2 days. Total body clearance was 41±19 ml/h.
No clinically relevant influence of body weight or gender on distribution volume or clearance has been observed in adult patients. Elimination half-life was not influenced by age, gender, or race.
The pharmacokinetics of basiliximab were assessed in 39 paediatric de novo renal transplantation patients. In infants and children (age 1–11 years, n=25), the steady-state distribution volume was 4.8±2.1 l, half-life was 9.5±4.5 days and clearance was 176 ml/h. Distribution volume and clearance are reduced by about 50% compared to adult renal transplantation patients. Disposition parameters were not influenced to a clinically relevant extent by age (1–11 years), body weight (9–37 kg) or body surface area (0.44–1.20m²) in this age group. In adolescents (age 12–16 years, n=14), the steady-state distribution volume was 7.8±5.1 l, half-life was 9.1±3.9 days and clearance was 31±19 ml/h. Disposition in adolescents was similar to that in adult renal transplantation patients. The relationship between serum concentration and receptor saturation was assessed in 13 patients and was similar to that characterised in adult renal transplantation patients.
No toxicity was observed when rhesus monkeys received intravenous doses of either up to 5 mg/kg basiliximab twice weekly for 4 weeks followed by an 8-week withdrawal period or 24 mg/kg basiliximab weekly for 39 weeks followed by a 13-week withdrawal period. In the 39-week study, the highest dose resulted in approximately 1,000 times the systemic exposure (AUC) observed in patients given the recommended clinical dose together with concomitant immunosuppressive therapy.
No maternal toxicity, embryotoxicity, or teratogenicity was observed in cynomolgous monkeys following injections of up to 5 mg/kg basiliximab administered twice weekly during the organogenesis period.
No mutagenic potential was observed in vitro.
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