Efficacy of Neoral in the immediate postoperative period in children post-liver transplantation.

Abstract

Cyclosporine (Sandimmune) is an effective immunosuppressive drug but may be poorly absorbed in the early postoperative period after liver transplantation, exposing the recipient to an increased risk for rejection. Neoral is a new oral formulation of cyclosporine that uses a mixture of surfactant, lipophilic, and hydrophilic solvents to permit microemulsification that leads to potentially better absorption. This oral drug has not been evaluated in children immediately posttransplantation. The aim of this study was to evaluate the pharmacokinetics, bioavailability, and safety of Neoral during the first week post-liver transplantation in children. Twelve children, 8 boys and 4 girls, with a median age of 2.6 years (range, 1 to 8 years) were administered Neoral within 12 hours posttransplantation. Pharmacokinetic profiles were performed over a 12-hour period on each child on days 1, 3, and 5 and twice-daily trough levels were obtained on days 2, 4, 6, and 7. The maximum concentration (Cmax), time to reach Cmax (Tmax), 12-hour trough levels, and area under the curve were calculated, and rejection episodes and adverse events were documented over a 12-week period. Neoral was well absorbed, even on the first postoperative day. After the introduction of enteral feeding, the peak levels increased (Cmax, 655 ng/mL) and were achieved significantly sooner (Tmax, 2 hours). There was no significant difference in drug exposure between days 1, 3, and 5 (P > .05). The incidence of acute rejection was 25% and hypertension was reported in 4 of 12 patients during the first week. Neoral was well absorbed in the early post-liver transplantation period, provided effective immunosuppression, and was not associated with a high incidence of adverse events or toxicity. The introduction of enteral feeding improved absorption.