Therapeutic drug monitoring of Voriconazole in liver transplant patients
10.3760/cma.j.cn114452-20240628-00337
- VernacularTitle:伏立康唑在肝移植术后感染患者中的治疗药物监测
- Author:
Junlan LIU
1
;
Yan SONG
1
;
Jie ZHANG
1
;
Min LI
1
Author Information
1. 上海交通大学医学院附属仁济医院检验科，上海 200127
- Publication Type:Journal Article
- Keywords:
Mycosis;
Invasive fungal diseases;
Voriconazole;
Liver transplantation;
Therapeutic drug monitoring;
Liquid chromatography tandem mass spectrometry
- From:
Chinese Journal of Laboratory Medicine
2025;48(3):346-351
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To assess the clinical application of voriconazole therapeutic drug monitoring in the individualized dosing of liver transplant recipients, aiming to optimize its therapeutic efficacy and safety.Methods:This is a single-center, case-control study that collected data from 55 liver transplant recipients at Renji Hospital, Shanghai Jiao Tong University School of Medicine, between August 2, 2019, and May 28, 2023. Among the participants, 33 were male and 22 were female, with an average age of (41.94±22.12) years. All patients received voriconazole, with a total of 235 drug concentration tests conducted. The concentrations of voriconazole were measured by liquid chromatography-tandem mass spectrometry. The study analyzed the correlation between different drug concentration levels and efficacy outcomes (negative fungal culturing result) and hepatoxicity (ALT, AST, and ALP exceeding three times the upper limit of normal). Factors influencing voriconazole concen tration levels were assessed using multiple linear regression analysis.Results:The coefficient of variation ( CV) for inter-individuals and intra-individuals voriconazole blood concentration was 94% and 58%, respectively. The difference in globulin levels among three groups with different drug concentrations (<1 μg/ml, 1-5.5 μg/ml,>5.5 μg/ml) was statistically significant ( H=8.65, P=0.013). Receiver operating characteristic curve analysis indicated that the risk of treatment failure increased when the trough concentration was<1.0 μg/ml, with an area under the curve (AUC) of 0.75; the risk of hepatotoxicity increased when the drug concentration was>4.4 μg/ml (AUC=0.62). Multiple linear regression analysis showed that the combined use of proton pump inhibitors (| t|=8.07, P<0.001) and other antifungal agents (| t|=3.82, P<0.001) was significantly positively correlated with voriconazole concentration, while the use of glucocorticoids (| t|=5.60, P<0.001) and antiviral drugs (| t|=3.59, P<0.001) was significantly negatively correlated with voriconazole concentration. Conclusion:There is significant inter-individual variability in voriconazole blood concentrations among liver transplant recipients, influenced by the mode of administration and types of concomitant medications. Maintaining blood concentrations within the range of 1.0-4.4 μg/ml can optimize therapeutic efficacy while reducing the occurrence of adverse effects.
