Nof-11: A one-year pediatric randomized double-blind comparison of neoral versus sandimmune in orthotopic liver transplantation

Background. Although cyclosporine (CsA) has been a mainstay in liver transp lantation immunosuppression the original formulation [Sandimmune (SIM)] has variable absorption, particularly in children. Neoral is a new formulation of CsA that may have improved biovailability that would be advantageous in children. This study was undertaken to assess the pharmacokinetics (PK) an d effects on outcome of Neoral versus Sandimmune (SIM) in primary pediatric liver transplant recipients. Methods. Thirty-two patients were randomized to receive Neoral (17 patients ) or SIM (15 patients) in the early posttransplant period (days 1-7) in a d ouble-blind fashion. Intravenous CsA was instituted immediately posttranspl ant followed by Neoral or SIM as soon as the patient was tolerating oral fl uids (days 1-7), PK were compared after the first dose (1-7 days), 3 weeks, and 6 and 12 months posttransplant. In addition, side effects, effect of a ge and food on absorption, and rejection episodes were assessed by intent t o treat analysis, Notable characteristics of this study include the use of a central laboratory for all sample analyses and the assessment of renal fu nction using radioisotopic evaluation of glomerular filtration rates. Results. At baseline the two groups were comparable. Neoral resulted in hig her peak levels of CsA and total drug exposure with comparable time to peak drug levels at days 1-7 and week 3, This trend was maintained at 6 and 12 months. Time on i.v. CsA was reduced in the Neoral group (8.4 vs. 11.1 days ) and the weight adjusted daily dose of SIM required to achieve target trou gh levels was about 2-fold more than Neoral from day 22 onward. In addition , biopsy proven and treated and steroid-resistant rejection episodes were f ewer in the Neoral group (6 vs. 12; P=0.01 and 1 vs. 8: P=0.004, respective ly). Side effects were comparable in both treatment groups. Conclusions. Neoral was well tolerated and had greater biovailability than SIM without any increase in the incidence of side effects. In addition fewe r episodes of rejection were observed with Neoral versus SIM. We conclude t hat Neoral is the CsA formulation of choice for use in pediatric liver tran splant recipients.