New oral formulation of cyclosporin A (Neoral) pharmacokinetics in allogeneic bone marrow transplant recipients

Cyclosporin A (CsA) absorption is variable in bone marrow transplant (BMT) patients compromising the efficacy of graft-versus-host disease prevention. Neoral, a new microemulsion formulation of CsA which has an improved bioavailibility, increases intestinal absorption of the drug with less variable pharmacokinetic parameters in non-BMT patients. In order to predict the best dosage of Neoral when patients are switched from i.v. to oral administration we performed a randomised study comparing two oral doses, either the same or twice the last i.v. dose used after BMT. Fourteen adults were randomised around day 25 after BMT. Whole blood CSA concentrations were measured 2 and 12 h after the oral administration of Neoral on days 0, 7 and 14 to determine residual and maximum concentration, and modified whenever necessary to maintain blood level CsA concentration within therapeutic range (150–250 ng/ml). We found that patients who received twice the last i.v. dose had better concentrations than patients from the other group while toxicity was identical in both groups. We conclude that doubling the last i.v. dose during the switch to oral administration of Neoral gives the best therapeutic range concentration and should be recommended for graft-versus-host prevention. Bone Marrow Transplantation (2000) 25, 965–968.