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

G. Dotti, F. Gaspari, R. Caruso, N. Perico, G. Remuzzi, T. Barbui, A. Rambaldi

Research output: Contribution to journalArticlepeer-review

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 Cmax (1027±203 vs. 1514±231 ng/mL). In all patients to whom 7.5 mg/kg/day of Neoral™ were given, Ctrough 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 Ctrough levels without significant renal toxicity.

Original languageEnglish
Pages (from-to)311-315
Number of pages5
JournalHaematologica
Volume86
Issue number3
Publication statusPublished - 2001

Keywords

  • Allogeneic bone marrow transplantation
  • Cyclosporin-A
  • Graft-versus-host disease
  • Immunosuppression

ASJC Scopus subject areas

  • Hematology

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