Optimal Post-Dose Levels of Cyclosporine A at a Higher Peak Concentration Are Correlated with the Area Under the Concentration-Time Curve of Twice-Daily Infusion and Oral Administration in Allogeneic Hematopoietic Stem Cell Transplantation.

Cyclosporine A (CyA), a calcineurin inhibitor, is widely used as an immunosuppressor for the prevention of acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation (alloHSCT). However, the optimal regimen of CyA has not yet been unequivocally established. Among liver transplant patients, it is important to maintain a peak CyA concentration and to monitor area under the concentration-time curve (AUC) and 2 h after CyA dosing (C2) for prophylaxis against graft rejection. We investigated the pharmacokinetics of CyA delivered by twice-daily infusion and oral administration maintained with a peak level above 1000 ng/ml to keep AUC 0-24 higher than 10000 ng-h/ml in 10 patients with hematological malignancy who underwent alloHSCT.

CyA was started as a twice-daily infusion at 1.5 mg/kg and then orally administered at twice the infusion dose in order to maintain the trough blood concentration between 200 and 500 ng/ml and with a peak level above 1000 ng/ml. Serial blood samples were collected at 0, 1, 2, 3, 5, 8, and 12 h after CyA dosing (C0,C1,C2,C3,C5,C8,C12) on days 14-21 after transplantation and on days 7-14 after switching to oral administration, and the AUC was calculated.

The mean AUC0-12 for twice-daily infusion and oral administration was 7443±998.5 ng-h/ml and 7185±1714 ng-h/ml, respectively. Among all the patients, the AUC0-24 for both CyA twice-daily infusion and oral administration was higher than 10000 ng-h/ml. Two close relationships were observed between AUC0-12 and the C3 level for infusion and between AUC0-12 and the C8 level for oral administration. Engraftment was achieved in all cases, and two patients suffered from grade 2 aGVHD. None of the patients had grades 3-4 aGVHD or other serious complications.

This strategy was well tolerated, and the C3 level for twice-daily infusion and the C8 level for oral administration were the optimal points for monitoring of CyA concentration in the early phase of alloHSCT.

No relevant conflicts of interest to declare.