Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation

We investigated the serial changes in the blood CsA concentration during the switch from continuous intravenous infusion to twice-daily oral administration in allogeneic hematopoietic stem cell transplant recipients (n=12). The microemulsion form of CsA, Neoral, was started at twice the last dose in intravenous infusion in two equally divided doses. The area under the concentration-time curve during oral administration (AUC PO) was significantly higher than the AUC during intravenous infusion (AUC IV) (median 7508 vs 6705 ng/ml × h, P=0.050). The median bioavailability of Neoral, defined as (AUC PO /DOSE PO) divided by (AUC IV /DOSE IV), was 0.685 (range, 0.45-1.04). Concomitant administration of oral voriconazole (n=4) significantly increased the bioavailability of Neoral (median 0.87 vs 0.54, P=0.017), probably due to the inhibition of gut CYP3A4 by voriconazole. Although the conversion from intravenous to oral administration of CsA at a ratio of 1:2 seemed to be appropriate in most patients, a lower conversion ratio may be better in patients taking oral voriconazole. To obtain a similar AUC, the target trough concentrations during twice-daily oral administration should be halved compared with the target concentration during continuous infusion.