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

Abstract

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 Cmax 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.