A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation

GUO Dongjie; LI Pengmei; CHEN Wenqian; LIU Lihong

doi:10.6039/j.issn.1001-0408.2023.20.13

您当前的位置：

首页 >

文章列表页 >

A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation

更新时间：2025-09-27

- A real-world survey of the effect of voriconazole on tacrolimus blood concentration after lung transplantation
- ZHONGGUO YAOFANG Vol. 34, Issue 20, Pages: 2519-2524(2023)
- 作者机构：
  
  中日友好医院药学部，北京　100029
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.20.13
  CLC： R969.2;R969.3
- Received：08 May 2023，
  
  Revised：2023-07-28，
  
  Accepted：28 July 2023，
  
  Published：30 October 2023
- 稿件说明：
移动端阅览
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[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[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

Keywords

references

CHAMBERS D C ， CHERIKH W S ， GOLDFARB S B ， et al . The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation：thirty-fifth adult lung and heart-lung transplant report-2018；focus theme：multiorgan transplantation [J ] . J Heart Lung Transplant ， 2018 ， 37 （ 10 ）： 1169 - 1183 .

SINGER J P ， SINGER L G . Quality of life in lung transplantation [J ] . Semin Respir Crit Care Med ， 2013 ， 34 （ 3 ）： 421 - 430 .

NEOFYTOS D ， FISHMAN J A ， HORN D ， et al . Epide-miology and outcome of invasive fungal infections in solid organ transplant recipients [J ] . Transpl Infect Dis ， 2010 ， 12 （ 3 ）： 220 - 229 .

HUSAIN S ， CAMARGO J F . Invasive aspergillosis in solid-organ transplant recipients：guidelines from the American Society of Transplantation Infectious Diseases Community of Practice [J ] . Clin Transplant ， 2019 ， 33 （ 9 ）： e13544 .

HOSSEINI-MOGHADDAM S M ， OUÉDRAOGO A ， NAYLOR K L ， et al . Incidence and outcomes of invasive fungal infection among solid organ transplant recipients：a population-based cohort study [J ] . Transpl Infect Dis ， 2020 ， 22 （ 2 ）： e13250 .

PAPPAS P G ， ALEXANDER B D ， ANDES D R ， et al . Invasive fungal infections among organ transplant reci-pients：results of the Transplant-Associated Infection Surveillance Network（TRANSNET） [J ] . Clin Infect Dis ， 2010 ， 50 （ 8 ）： 1101 - 1111 .

IMAMURA C K ， FURIHATA K ， OKAMOTO S ， et al . Impact of cytochrome P450 2C19 polymorphisms on the pharmacokinetics of tacrolimus when coadministered with voriconazole [J ] . J Clin Pharmacol ， 2016 ， 56 （ 4 ）： 408 - 413 .

GROLL A H ， TOWNSEND R ， DESAI A ， et al . Drug-drug interactions between triazole antifungal agents used to treat invasive aspergillosis and immunosuppressants metabolized by cytochrome P450 3A4 [J/OL ] . Transpl Infect Dis ， 2017 ， 19 （ 5 ）（ 2017-09-28 ）[ 2023-03-01 ] . https：//pubmed.ncbi.nlm.nih.gov/28722255/.DOI：10.1111/tid.12751 https://pubmed.ncbi.nlm.nih.gov/28722255/.DOI:10.1111/tid.12751 .

王晓雪，陈文倩，刘慧芳，等 . 利用同位素稀释质谱法测定人血浆中伏立康唑及治疗药物监测实践 [J ] . 中国药师， 2019 ， 22 （ 7 ）： 1189 - 1192 .

WANG X X ， CHEN W Q ， LIU H F ， et al . Quantification of voriconazole in human plasma by UPLC-MS/MS and its application in therapeutic drug monitoring [J ] . China Pharmacist ， 2019 ， 22 （ 7 ）： 1189 - 1192 .

BRUNET M ， VAN GELDER T ， ÅSBERG A ， et al . Therapeutic drug monitoring of tacrolimus-personalized therapy：second consensus report [J ] . Ther Drug Monit ， 2019 ， 41 （ 3 ）： 261 - 307 .

陈文倩，张雷，张弋，等 . 实体器官移植他克莫司个体化治疗专家共识 [J ] . 中国医院用药评价与分析， 2021 ， 21 （ 12 ）： 1409 - 1424 .

CHEN W Q ， ZHANG L ， ZHANG Y ， et al . Expert consensus on individual treatment of tacrolimusin solid organ transplantation [J ] . Eval Anal Drug Use Hosp China ， 2021 ， 21 （ 12 ）： 1409 - 1424 .

PATTERSON T F ， 3rd THOMPSON G R ， DENNING D W ， et al . Practice guidelines for the diagnosis and management of aspergillosis：2016 update by the Infectious Di-seases Society of America [J ] . Clin Infect Dis ， 2016 ， 63 （ 4 ）： e1 - e60 .

KULKARNI H S ， WITT C A . Voriconazole in lung transplant recipients： how worried should we be? [J ] . Am J Transplant ， 2018 ， 18 （ 1 ）： 5 - 6 .

CHANG H H ， LEE N Y ， KO W C ， et al . Voriconazole inhibition of tacrolimus metabolism in a kidney transplant recipient with fluconazole-resistant cryptococcal meningitis [J ] . Int J Infect Dis ， 2010 ， 14 （ 4 ）： e348 - e350 .

SUETSUGU K ， MORI ， YAMAMOTO N ， et al . Impact of CYP3A5，POR，and CYP2C19 polymorphisms on trough concentration to dose ratio of tacrolimus in allogeneic hematopoietic stem cell transplantation [J ] . Int J Mol Sci ， 2019 ， 20 （ 10 ）： 2413 .

VANHOVE T ， BOUWSMA H ， HILBRANDS L ， et al . Determinants of the magnitude of interaction between tacrolimus and voriconazole/posaconazole in solid organ reci-pients [J ] . Am J Transplant ， 2017 ， 17 （ 9 ）： 2372 - 2380 .

MORI T ， KATO J ， YAMANE A ， et al . Drug interaction between voriconazole and tacrolimus and its association with the bioavailability of oral voriconazole in recipients of allogeneic hematopoietic stem cell transplantation [J ] . Int J Hematol ， 2012 ， 95 （ 5 ）： 564 - 569 .

VENKATARAMANAN R ， ZANG S M ， GAYOWSKI T ， et al . Voriconazole inhibition of the metabolism of tacrolimus in a liver transplant recipient and in human liver microsomes [J ] . Antimicrob Agents Chemother ， 2002 ， 46 （ 9 ）： 3091 - 3093 .

ZHAO Y C ， XIAO C L ， HOU J J ， et al . The effect of voriconazole on tacrolimus in kidney transplantation reci-pients：a real-world study [J ] . Pharmaceutics ， 2022 ， 14 （ 12 ）： 2739 .

CHEN W Q ， WANG X X ， LI B ， et al . Effects of vorico-nazole exposure on the pharmacokinetics of tacrolimus in lung transplantation patients，based on therapeutic drug monitoring data [J ] . J Clin Pharmacol ， 2022 ， 62 （ 10 ）： 1310 - 1320 .

HOHMANN N ， KOCHEISE F ， CARLS A ， et al . Dose-dependent bioavailability and CYP3A inhibition contri-bute to non-linear pharmacokinetics of voriconazole [J ] . Clin Pharmacokinet ， 2016 ， 55 （ 12 ）： 1535 - 1545 .

JOHNSON T N ， SALEM F ， JAMEI M ， et al . Prediction of voriconazole non-linear pharmacokinetics using a paediatric physiologically based pharmacokinetic modelling approach [J ] . Clin Pharmacokinet ， 2015 ， 54 （ 5 ）： 567 - 568 .

KIM Y ， RHEE S J ， PARK W B ， et al . A personalized CYP2C19 phenotype-guided dosing regimen of vorico-nazole using a population pharmacokinetic analysis [J ] . J Clin Med ， 2019 ， 8 （ 2 ）： 227 .

WEHBE E ， DUNCAN A E ， DAR G ， et al . Recovery from AKI and short- and long-term outcomes after lung transplantation [J ] . Clin J Am Soc Nephrol ， 2013 ， 8 （ 1 ）： 19 - 25 .

SIKMA M A ， HUNAULT C C ， VAN DE GRAAF E A ， et al . High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury [J ] . Eur J Clin Pharmacol ， 2017 ， 73 （ 5 ）： 573 - 580 .

ZAPATA C M ， IBRAHIM H N . Kidney disease after heart and lung transplantation [J ] . Methodist Debakey Cardiovasc J ， 2022 ， 18 （ 4 ）： 34 - 40 .

PLOSKER G L ， FOSTER R H . Tacrolimus：a further update of its pharmacology and therapeutic use in the ma-nagement of organ transplantation [J ] . Drugs ， 2000 ， 59 （ 2 ）： 323 - 389 .

官东秀，冯祚臻，俸小平，等 . 伏立康唑药物不良反应文献分析 [J ] . 齐鲁药事， 2009 ， 28 （ 8 ）： 507 - 508 .

GUAN D X ， FENG Z Z ， FENG X P ， et al . Literature analysis of adverse drug reactions of voriconazole [J ] . Qilu Pharm Aff ， 2009 ， 28 （ 8 ）： 507 - 508 .

Views

225

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Research progress in pharmacokinetics and therapeutic drug monitoring of tyrosine kinase inhibitors in the treatment of gastrointestinal stromal tumors

Dose-adjusted concentrations of Posaconazole oral suspension in hematopoietic stem cell transplantation patients and analysis of the influential factors

Research progress in pharmacokinetics/pharmacodynamics and therapeutic drug monitoring of biapenem

Research progress in pharmacokinetics/pharmacodynamics and drug use of meropenem in special population

Multi-centre survey and analysis of individual therapy of antimicrobial agents in children

Related Author

SUN Luning

HUANG Qiongye

WANG Yongqing

LIU Yi

ZHAO Yang

SHU Yishuo

DONG Zhonghua

YI Qiaoyan

Related Institution

Clinical Pharmacology Center， the First Affiliated Hospital of Nanjing Medical University

School of Pharmacy， Nanjing Medical University

Dept. of Hematology， the First Affiliated Hospital of Shandong First Medical University（Shandong Provincial Qianfoshan Hospital）

Dept. of Clinical Pharmacy， the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital）/Shandong Engineering and Technology Research Center for Pediatric Drug Clinical Evaluation and Development/Shandong Medicine and Health Key Laboratory of Clinical Pharmacy

Dept. of Pediatrics， the First Affiliated Hospital of Shandong First Medical University （Shandong Provincial Qianfoshan Hospital）/Shandong Engineering and Technology Research Center for Pediatric Drug Clinical Evaluation and Development

⁰