EFFICACY OF NEORAL IN THE IMMEDIATE POSTOPERATIVE PERIOD IN CHILDREN POST LIVER-TRANSPLANTATION

Cyclosporine (Sandimmune) is an effective immunosuppressive drug but m ay be poorly absorbed in the early postoperative period after liver tr ansplantation, exposing the recipient to an increased risk for rejecti on. Neoral is a new oral formulation of cyclosporine that uses a mixtu re of surfactant, lipophilic, and hydrophilic solvents to permit micro emulsification that leads to potentially better absorption. This oral drug has not been evaluated in children immediately posttransplantatio n. The aim of this study was to evaluate the pharmacokinetics, bioavai lability, and safety of Neoral during the first week post-liver transp lantation in children. Twelve children, 8 boys and 4 girls, with a med ian age of 2.6 years (range, 1 to 8 years) were administered Neoral wi thin 12 hours posttransplantation. Pharmacokinetic profiles were perfo rmed 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 (C-max), time to reach Cmax (T-max), 12-hour trough lev els, and area under the curve were calculated, and rejection episodes and adverse events were documented over a 12-week period. Neoral was w ell absorbed, even on the first postoperative day. After the introduct ion of enteral feeding, the peak levels increased (C-max, 655 ng/mL) a nd were achieved significantly sooner (T-max, 2 hours). There was no s ignificant difference in drug exposure between days 1, 3, and 5 (P > . 05). The incidence of acute rejection was 25% and hypertension was rep orted in 4 of 12 patients during the first week. Neoral was well absor bed in the early post-liver transplantation period, provided effective immunosuppression, and was not associated with a high incidence of ad verse events or toxicity. The introduction of enteral feeding improved absorption. (C) 1998 by the American Association for the Study of Liv er Diseases.