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米卡芬净在接受异基因造血干细胞移植患者中的药代动力学

Pharmacokinetics of micafungin in patients undergoing allogeneic hematopoietic stem cell transplantation.

作者信息

Oshima K, Kanda Y, Kako S, Ohno K, Kishino S, Kurokawa M

机构信息

Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.

出版信息

Transpl Infect Dis. 2013 Jun;15(3):323-7. doi: 10.1111/tid.12070. Epub 2013 Apr 11.

Abstract

OBJECTIVES

Micafungin (MCFG) is an antifungal agent that is widely used for the treatment of invasive fungal infection. Although the pharmacokinetics of MCFG is considered to depend on the hepatic metabolism, the impact of hepatic function on the pharmacokinetics of MCFG has been inconsistent among previous studies. The object of this study was to evaluate the relationship between plasma MCFG concentration and clinical and laboratory data.

PATIENTS AND METHODS

We examined the plasma concentration of MCFG in 10 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). MCFG at 150 mg/day was administered intravenously a median of 58.5 days after HSCT. Trough and peak concentrations of MCFG (Cmin and Cmax) were measured at a median of 5.5 days after the first administration of MCFG.

RESULTS

The presence of graft-versus-host disease involving the liver at blood sampling was associated with significantly higher Cmin and Cmax of MCFG. Among the laboratory data, Cmin and Cmax were significantly higher in patients with severely impaired hepatic function defined as serum total bilirubin (TBi) level >5 mg/dL and/or serum gamma-glutamyltransferase (γ-GTP) level >500 IU/L, but the presence of mildly impaired hepatic function defined as serum TBi level >2 mg/dL and/or serum γ-GTP level >200 IU/L did not affect Cmin and Cmax. Renal function did not show significant impact on Cmin and Cmax.

CONCLUSION

These findings suggest that the pharmacokinetics of MCFG is affected only by severely impaired liver function.

摘要

目的

米卡芬净(MCFG)是一种广泛用于治疗侵袭性真菌感染的抗真菌药物。尽管MCFG的药代动力学被认为依赖于肝脏代谢,但先前研究中关于肝功能对MCFG药代动力学的影响并不一致。本研究的目的是评估血浆MCFG浓度与临床及实验室数据之间的关系。

患者与方法

我们检测了10例接受异基因造血干细胞移植(HSCT)患者的血浆MCFG浓度。HSCT后中位58.5天,静脉给予MCFG 150mg/天。在首次给予MCFG后中位5.5天测量MCFG的谷浓度和峰浓度(Cmin和Cmax)。

结果

采血时存在累及肝脏的移植物抗宿主病与MCFG显著更高的Cmin和Cmax相关。在实验室数据中,血清总胆红素(TBi)水平>5mg/dL和/或血清γ-谷氨酰转移酶(γ-GTP)水平>500IU/L定义为肝功能严重受损的患者,其Cmin和Cmax显著更高,但血清TBi水平>2mg/dL和/或血清γ-GTP水平>200IU/L定义为肝功能轻度受损的情况并不影响Cmin和Cmax。肾功能对Cmin和Cmax无显著影响。

结论

这些发现表明MCFG的药代动力学仅受严重肝功能损害的影响。

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