Abstract • 158

Cyclosporin A (CsA) is an immunosuppressive agent used to prevent or treat graft-versus-host disease in patients undergoing stem cell transplantation. Despite a long time of use, there are limited data on the pharmacokinetiks of CsA in children after allogeneic stem cell transplantation. In this report we present the results of a prospective randomized pharmacokinetic study of three different CsA formulations: intravenous CsA, Sandimmun® and Sandimmun Optoral® (Novartis Pharma GmbH). Between 95/11 and 98/01 20 children (median age 6.4) who underwent allogeneic stem cell transplantation were randomized in a crossover allocation to receive each formulation on two separate occasions in the sequence Sandimmun/Optoral or Optoral/Sandimmun when oral intake was possible. The second oral conversion was around day +60 after stem cell transplantation. CsA concentration in whole blood samples were measured by fluorescence-polarization-immunoassay. For each formulation we analyzed trough and peak concentration (Cmin, Cmax), area under the curve (AUC), time of peak concentration (tmax) and clearance (CI). Our results showed no significant difference in tmax, Cmax and AUC between the two oral formulations. Cmax and AUC were significant higher in the intravenous formulation. The interindividual variability was very high by Optoral in comparison to Sandimmun and the intravenous CsA formulation. We conclude that the high interindividual variability by Optoral with sometimes very high Cmax levels could be associated with an increase of noticed neurological side-effects. This high Cmax levels were not detected by our 12h trough level monitoring. An improvement of monitoring of CsA levels under treatment could be possible with a limited sampling model.