伏立康唑对肺移植患者术后他克莫司血药浓度影响的真实世界研究

郭冬杰; 李朋梅; 陈文倩; 刘丽宏

doi:10.6039/j.issn.1001-0408.2023.20.13

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伏立康唑对肺移植患者术后他克莫司血药浓度影响的真实世界研究

药物与临床 | 更新时间：2023-10-25

- 伏立康唑对肺移植患者术后他克莫司血药浓度影响的真实世界研究
- A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation
- 中国药房 2023年34卷第20期页码：2519-2524
- 作者机构：
  
  中日友好医院药学部，北京　100029
- 作者简介：
  
  副主任药师，硕士。研究方向：抗感染药物、ICU临床药学、抗菌药物治疗药物监测。E-mail：guodongjie1223@163.com
  主任药师，博士。研究方向：代谢性疾病的新药筛选与发现、药理学评价及疾病机制。E-mail：hongllh@126.com
- 基金信息：
  
  首都卫生发展科研专项项目(首发2020-1-2031)
- DOI：10.6039/j.issn.1001-0408.2023.20.13
  中图分类号： R969.2;R969.3
- 纸质出版日期：2023-10-30，
  
  收稿日期：2023-05-08，
  
  修回日期：2023-07-28，
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郭冬杰,李朋梅,陈文倩等.伏立康唑对肺移植患者术后他克莫司血药浓度影响的真实世界研究 ^Δ[J].中国药房,2023,34(20):2519-2524.

GUO Dongjie,LI Pengmei,CHEN Wenqian,et al.A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation[J].ZHONGGUO YAOFANG,2023,34(20):2519-2524.
郭冬杰,李朋梅,陈文倩等.伏立康唑对肺移植患者术后他克莫司血药浓度影响的真实世界研究 ^Δ[J].中国药房,2023,34(20):2519-2524. DOI： 10.6039/j.issn.1001-0408.2023.20.13.

GUO Dongjie,LI Pengmei,CHEN Wenqian,et al.A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation[J].ZHONGGUO YAOFANG,2023,34(20):2519-2524. DOI： 10.6039/j.issn.1001-0408.2023.20.13.

摘要

目的

为肺移植患者联用伏立康唑后他克莫司的剂量调整提供依据。

方法

回顾性收集2020年1月至2022年12月在我院联合使用了伏立康唑和他克莫司的肺移植患者资料。采用SPSS 21.0软件分析伏立康唑对他克莫司谷浓度、日剂量和标准化血药浓度的影响，并对可能影响他克莫司标准化血药浓度的因素进行多元线性回归分析。

结果

共纳入肺移植患者153例。联用伏立康唑后，患者使用的他克莫司平均日剂量从3.37 mg降至0.76 mg，谷浓度和标准化血药浓度均显著升高（

＜0.000 1）。伏立康唑日剂量与他克莫司标准化血药浓度呈显著负相关（

＝0.000 1，

＝－0.224）；伏立康唑谷浓度与他克莫司谷浓度（

＜0.000 1，

＝0.316）、标准化血药浓度（

＜0.000 1，

＝0.249）均呈显著正相关。联用伏立康唑后，单肺移植患者的他克莫司标准化血药浓度显著高于双肺移植患者，且口服伏立康唑后他克莫司的标准化血药浓度显著高于静脉滴注伏立康唑后（

＜0.05）；大部分肝肾功能指标均无显著变化。多因素回归分析结果显示，伏立康唑谷浓度对他克莫司标准化血药浓度具有显著影响（

＜0.001）。

结论

伏立康唑谷浓度对他克莫司的血药浓度和剂量调整影响较大，是影响他克莫司血药浓度的独立因素。临床应在联合伏立康唑后对他克莫司减量，同时对两药进行治疗药物监测。

Abstract

OBJECTIVE

To provide a reference for the dose adjustment of tacrolimus in patients who underwent lung transplantation after combined use of voriconazole.

METHODS

The clinical data of lung transplantation patients who used voriconazole and tacrolimus in our hospital from January 2020 to December 2022 were collected retrospectively. The effects of voriconazole on the valley concentration， daily dose and standardized blood concentration of tacrolimus were analyzed by using SPSS 21.0 software； multiple linear regression analysis was conducted for the factors that may affect the standardized blood concentration of tacrolimus.

RESULTS

A total of 153 lung transplantation patients were included. After the combination of voriconazole， the average daily dose of tacrolimus decreased from 3.37 mg to 0.76 mg， and valley concentration and standardized blood concentration were increased significantly （

＜0.000 1）. The average daily dose of voriconazole was negatively correlated with the standardized blood drug concentration of tacrolimus （

＝0.000 1，

＝－0.224）. The valley concentration of voriconazole was positively correlated with valley concentration （

＜0.000 1，

＝0.316） and standardized blood concentration （

＜0.000 1，

＝0.249） of tacrolimus. After combination with voriconazole， the standardized blood drug concentration of patients who underwent single lung transplantation was significantly higher than those who underwent double lung transplantation， and the standardized blood concentration of tacrolimus after oral administration of voriconazole was significantly higher than after intravenous drip of voriconazole （

＜0.05）. Most liver and kidney function indicators showed no significant changes. The results of multiple factor regression analysis showed that the valley concentration of voriconazole had a significant impact on the standardized blood concentration of tacrolimus （

＜0.001）.

CONCLUSIONS

The valley concentration of voriconazole has greatest influence on the blood concentration and dose adjustment of tacrolimus， which is an independent influencing factor. In clinical practice， the dose of tacrolimus should be reduced in combination with voriconazole， and therapeutic drug monitoring should be conducted for both drugs.

关键词

伏立康唑他克莫司肺移植血药浓度治疗药物监测

Keywords

tacrolimuslung transplantationblood concentrationtherapeutic drug monitoring

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