The pharmacokinetics of oral cyclosporin a (neoral) during the first month after bone marrow transplantation

Abstract

THE USE of cyclosporin A (CyA) has been complicated by its large interand intra-patient pharmacokinetic variability, which is likely due to variability in intestinal absorption. Patients with impaired intestinal integrity may have additional problems with absorption of CsA, further complicating selection of a therapeutic dose. The pharmacokinetic variability observed for CsA has prompted monitoring of CsA in blood to ensure appropriate concentrations are attained. Sandimmune Neoral, a new preparation of CsA, is absorbed independent of a bile secretion in the gut and has increased absorption and less variable pharmacokinetic parameters compared to the older preparation (Sandimmune) in solid organ transplants. CsA is used extensively in bone marrow transplantation (BMT) both in children and adults. This population has significant differences compared to solid transplant patients in intestinal integrity, possibly affecting intestinal absorption of CsA. These differences include a mucositis secondary to the preparative regimen used in BMT resulting in diffuse inflammation of the intestinal tract. In addition, these patients develop graft-versus-host disease (GVHD) and viral infections of the intestinal tract resulting in diffuse inflammation affecting possibly absorption of CsA. In the BMT population, Sandimmune Neoral may provide improved absorption and increased blood concentrations, as well as better control of CsA pharmacokinetic variability potentially improving therapeutic efficacy of oral CsA.