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

Background and Objectives. A major problem encountered during oral cyclosporin-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 pharmacokinetics of Neoral™, a new water-free microemulsion formulation of CsA. Design and Methods. Eighteen patients aged over 18 were enrolled into the study. When able to eat normally after allo-BMT, patients received CsA orally and after 4 days a 12-hour CsA pharmacokinetic profile was constructed. Three patients received Sandimmune™ 10 mg/kg/day, 5 patients received Neoral™ 7.5 mg/kg/day and 10 patients Neoral™ 5 mg/kg/day. CsA concentration was analyzed on whole blood by high-performance liquid chromatography (HPLC). Results. Neoral™ showed concentration-time profiles characterized by a smooth and faster rise to the C_max value compared to that produced by Sandimmune™. The comparison between pharmacokinetic parameters obtained in patients receiving Neoral™ 5 mg/kg/day or 7.5 mg/kg/day showed a proportional increase of the AUC (4776±1084 vs. 7746±2006 ng/mL h) and C_max (1027±203 vs. 1514±231 ng/mL). In all patients to whom 7.5 mg/kg/day of Neoral™ were given, C_trough levels were always above the threshold of 200 ng/mL Interpretation and Conclusions. Our data suggest that oral administration of Neoral™ 7.5 mg/kg/day early after allo-BMT may represent an appropriate dose resulting in adequate CsA C_trough levels without significant renal toxicity.