Basiliximab in pediatric liver transplantation: A pharmacokinetic‐derived dosing algorithm

Abstract: The pharmacokinetics and immunodynamics of basiliximab were assessed in 37 pediatric de novo liver allograft recipients to rationally design a dose regimen for this age‐group. In part one of the study, patients were given 12 mg/m 2 basiliximab by bolus intravenous injection after organ perfusion and on day 4 after transplant. An interim pharmacokinetic evaluation supported a fixed‐dose approach for part two of the study in which infants and children received two 10‐mg doses of basiliximab and adolescents received two 20‐mg doses. Blood samples were collected over a 12‐week period for screening for anti‐idiotype antibodies and analysis of basiliximab and soluble interleukin‐2 receptor (IL‐2R) concentrations. Basiliximab clearance in infants and children < 9 yr of age (n = 30) was reduced by ≈ 50% compared with adults from a previous study and was independent of age to 9 yr, weight to 30 kg, and body surface area to 1.0 m 2 . Clearance in children and adolescents 9–14 yr of age (n = 7) approached or reached adult values. An average of 15% of the dose was eliminated via drained ascites fluid, and drug clearance via this route averaged 29% of total body clearance. Patients with > 5 L of ascites fluid drainage tended to have lower systemic exposure to basiliximab. CD25‐saturating basiliximab concentrations were maintained for 27 ± 9 days in part one of the study (mg/m 2 dosing) with infants exhibiting the lowest durations. CD25 saturation lasted 37 ± 11 days in part two of the study, based on the fixed‐dose regimen (p = 0.004 vs. mg/mg 2 dosing), but did not show the age‐related bias observed in part one of the study. Anti‐idiotype antibodies were detected in four patients, but this did not influence the clearance of basiliximab or duration of CD25 saturation. All 40 enrolled patients were included in the intent‐to‐treat clinical analysis. Episodes of acute rejection occurred in 22 patients (55%) during the first 12 months post‐transplant. Three patients experienced loss of their graft as a result of technical complications, and six patients died during the 12‐month study. Basiliximab was well tolerated by intravenous bolus injection, with no cytokine‐release syndrome or other infusion‐related adverse events. Hence, basiliximab was safe and well tolerated in pediatric patients undergoing orthotopic liver transplantation. To achieve similar basiliximab exposure as is efficacious in adults, pediatric patients < 35 kg in weight should receive two 10‐mg doses and those ≥ 35 kg should receive two 20‐mg doses of basiliximab by intravenous infusion or bolus injection. The first dose should be given within 6 h after organ perfusion and the second on day 4 after transplantation. A supplemental dose may be considered for patients with a large volume of drained ascites fluid relative to body size.