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Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants.

Abstract：

PURPOSE:The purpose of this study was to investigate the interactions of itraconazole (ITCZ) with orally administered calcineurin inhibitors (CNIs) in Japanese allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS:Sixteen HSCT patients (8 patients each receiving tacrolimus or cyclosporine) were enrolled. An ITCZ oral solution was administered from day 30 after the initiation of ITCZ administration as a loading dose. Before the co-administration of ITCZ and CNI and 1 week daily thereafter, whole blood ITCZ and CNI (tacrolimus or cyclosporine) concentrations were measured in samples taken just before (C0h) and 2 h (C2h) after CNI administration. RESULTS:The median dose-adjusted C0h values of tacrolimus and cyclosporine on day 7 after the start of ITCZ co-administration were 5.6- and 2.7-fold higher, respectively, than the corresponding values obtained before the initiation of ITCZ treatment. On day 7 after ITCZ treatment, the mean single dosages of tacrolimus and cyclosporine were reduced to 33.7 and 66.5 % of the dosages before ITCZ co-administration, respectively, to adjust the CNI target concentration. Although ITCZ co-administration did not alter the dose-adjusted C0h values of tacrolimus in a patient with a CYP3A5 1/ 1 allele, it did change this value of tacrolimus in patients with CYP3A5 3 alleles. However, in patients receiving cyclosporine, no such tendency was observed. CONCLUSION:The magnitude of the interaction between orally administered tacrolimus and ITCZ was significantly greater than that between cyclosporine and ITCZ. Prospective analysis of the CYP3A5 polymorphism may be important to ensure safe and reliable immunosuppressive therapy with tacrolimus in patients treated with ITCZ.

journal_name

Eur J Clin Pharmacol

journal_title

European journal of clinical pharmacology

authors

Nara M,Takahashi N,Miura M,Niioka T,Kagaya H,Fujishima N,Saitoh H,Kameoka Y,Tagawa H,Hirokawa M,Sawada K

doi

10.1007/s00228-013-1471-2

subject

Has Abstract

pub_date

2013-06-01 00:00:00

pages

1321-9

issue

eissn

0031-6970

issn

1432-1041

journal_volume

pub_type

临床试验,杂志文章

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Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants.