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

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.

journal_name

Bone Marrow Transplant

journal_title

Bone marrow transplantation

authors

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

doi

10.1038/bmt.2009.316

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

1088-94

issue

6

eissn

0268-3369

issn

1476-5365

pii

bmt2009316

journal_volume

45

pub_type

临床试验,杂志文章

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