| Title | Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation. | | Author(s) | Kimura S, Oshima K, Okuda S, Sato K, Sato M, Terasako K, Nakasone H, Kako S, Yamazaki R, Tanaka Y, Tanihara A, Higuchi T, Nishida J, Kanda Y | | Institution | Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. | | Source | Bone Marrow Transplant 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.Bone Marrow Transplantation advance online publication, 9 November 2009; doi:10.1038/bmt.2009.316. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19898510 |
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