造血干细胞移植儿童体内伏立康唑与钙调神经磷酸酶抑制剂的相互作用

Interaction between Voriconazole and Calcineurin Inhibitors in Children Undergoing Hematopoietic Stem Cell Transplantation

目的:评价接受造血干细胞移植(HSCT)患儿中伏立康唑与钙调神经磷酸酶抑制剂环孢素(CsA)或他克莫司(FK506)之间的相互作用。方法:采用前瞻性队列研究方法评估31例接受稳定剂量CsA或FK506并开始使用伏立康唑的同种异体HSCT患儿。在伏立康唑用药前和用药后5~8 d测定CsA或FK506的血药浓度,并在稳态下测定伏立康唑的血药浓度,评估伏立康唑给药前后CsA及FK506的血药浓度变化情况。结果:伏立康唑给药后,CsA的浓度/剂量(C/D)值增加了215.75%(10.16%~706.35%),FK506的C/D增加了239.24%(89.66%~615.00%)(P均<0.01)。伏立康唑对CsA和对FK506血药浓度的影响程度相当(P>0.05)。伏立康唑血药浓度与CsA的C/D增幅之间无相关性(P>0.05),而与FK506的C/D增幅呈正相关(P<0.05)。结论:HSCT患儿联用伏立康唑后,CsA与FK506的血药浓度明显增加,且增加幅度存在显著个体差异。

Objective: To evaluate the interaction between voliconazole and calcineurin inhibitors cyclosporine(CsA) or tacrolimus(FK506) in children undergoing hematopoietic stem cell transplantation(HSCT). Methods: A prospective cohort study method was used to evaluate 31 children with allogeneic HSCT who received a steady dose of CsA or FK506 and were started on voriconazole. The blood concentration of CsA or FK506 was measured before and after voriconazole administration of 5 to 8 d, the blood concentration of voriconazole were determined at the steady state, and the changes in blood concentration of CsA or FK506 before and after voriconazole administration were detected. Results: After voriconazole administration, the concentration/dose(C/D) values increased by 215.75%(from 10.16% to 706.35%) for CsA and 239.24%(from 89.66% to 615.00%) for FK506(P<0.01). Voriconazole had similar effects on CsA and FK506(P>0.05). There was no correlation between the blood concentration of voriconazole and the C/D increase of CsA(P>0.05), yet there was a positive correlation between the blood concentration of voriconazole and the C/D increase of FK506(P<0.05). Conclusion: The blood concentration of CsA and FK506 increase significantly after the combination of voriconazole in children with HSCT, and there are significant individual differences in the magnitude of the increase.