Pharmacokinetic study of the new cyclosporin-A formulation (Neoral (TM)) in adult allogeneic bone marrow transplant recipients

Background and Objectives. A major problem encountered during oral cyclospo rin-A (CsA) administration to prevent acute graft-versus-host-disease (GVHD ) after allogeneic bone marrow transplantation (allo-BMT) is its irregular pharmacokinetics. The aim of this study was to evaluate the pharmacokinetic s of Neoral(TM), a new water-free microemulsion formulation of CsA. Design and Methods. Eighteen patients aged over 18 were enrolled into the s tudy. When able to eat normally after allo-BMT, patients received CsA orall y and after 4 days a 12-hour CsA pharmacokinetic profile was constructed. T hree patients received Sandimmune(TM) 10 mg/kg/day, 5 patients received Neo ral(TM) 7.5 mg/kg/day and 10 patients Neoral(TM) 5 mg/kg/day, CsA concentra tion was analyzed on whole blood by high-performance liquid chromatography (HPLC). Results. Neoral(TM) showed concentration-time profiles characterized by a s mooth and faster rise to the C-max value compared to that produced by Sandi mmune(TM), The comparison between pharmacokinetic parameters obtained in pa tients receiving Neoral(TM) 5 mg/kg/day or 7.5 mg/kg/day showed a proportio nal increase of the AUC (4776+/-1084 vs. 7746+/-2006 ng/mL h) and C-max (10 27+/-203 vs. 1514+/-231 ng/mL), in all patients to whom 7.5 mg/kg/day of Ne oral(TM) were given, C-trough levels were always above the threshold of 200 ng/mL. Interpretation and Conclusions, Our data suggest that oral administration o f Neoral(TM) 7.5 mg/kg/day early after allo-BMT may represent an appropriat e dose resulting in adequate CsA C-trough levels without significant renal toxicity. (C) 2001, Ferrata Storti Foundation.