Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants
Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants
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DOI：
10.1007/s00228-013-1471-2
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发表时间：
2013-06-01
影响因子：
2.9
通讯作者：
Sawada, Kenichi
中科院分区：
文献类型：
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作者：
Nara, Miho;Takahashi, Naoto;Sawada, Kenichi
本研究的目的是探讨在日本异基因造血干细胞移植（HSCT）受者中伊曲康唑（ITCZ）与口服钙调磷酸酶抑制剂（CNIs）的相互作用。从ITCZ给药开始后第30天起，给予ITCZ口服溶液作为负荷剂量。在ITCZ和CNI联合给药前和此后每天1周，在CNI给药前（C-0 h）和给药后2 h（C-2 h）采集的样本中测量了他克莫司和环孢霉素（他克莫司或环孢霉素）的浓度。在开始ITCZ联合给药后第7天，他克莫司和环孢霉素的中位剂量调整C-0 h值分别高出5.6倍和2.7倍，与ITCZ治疗开始前获得的相应值相比。在ITCZ治疗后第7天，他克莫司和环孢素的平均单次剂量分别减少至ITCZ联合给药前剂量的33.7%和66.5%，以调整CNI目标浓度。尽管ITCZ联合给药并未改变具有CYP 3A 5 *1/*1等位基因的患者中他克莫司的剂量调整C-0 h值，但它确实改变了具有CYP 3A 5 *3等位基因的患者中他克莫司的该值。口服他克莫司和ITCZ之间的相互作用的程度显著大于环孢素和ITCZ之间的相互作用。对CYP 3A 5多态性的前瞻性分析对于确保ITCZ治疗患者的他克莫司免疫抑制治疗安全可靠可能很重要。
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.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 (C-0h) and 2 h (C-2h) after CNI administration.The median dose-adjusted C-0h 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 C-0h 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.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.