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

Bone Marrow Transplant. 2010 Jun;45(6):1088-94. doi: 10.1038/bmt.2009.316. Epub 2009 Nov 9.

Abstract

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 x 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Antifungal Agents
  • Area Under Curve
  • Biological Availability
  • Cyclosporine / pharmacokinetics*
  • Drug Synergism
  • Female
  • Graft vs Host Disease
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Immunosuppressive Agents
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Pyrimidines / therapeutic use
  • Transplantation, Homologous
  • Treatment Outcome
  • Triazoles / therapeutic use
  • Voriconazole
  • Young Adult

Substances

  • Antifungal Agents
  • Immunosuppressive Agents
  • Pyrimidines
  • Triazoles
  • Cyclosporine
  • Voriconazole