侵袭性真菌感染患者伏立康唑肝毒性的研究

王陶陶, 陈思颖, 尤海生, 董海燕, 王雪, 董亚琳

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (4) : 290-294.

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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (4) : 290-294. DOI: 10.11669/cpj.2018.04.010
论著

侵袭性真菌感染患者伏立康唑肝毒性的研究

  • 王陶陶a, 陈思颖a, 尤海生a, 董海燕a, 王雪b, 董亚琳a*
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Hepatotoxicity Study of Voriconazole Therapy in Patients with Invasive Fungal Infections

  • WANG Tao-taoa, CHEN Si-yinga, YOU Hai-shenga, DONG Hai-yana, WANG Xueb, DONG Ya-lina*
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摘要

目的 探讨伏立康唑治疗侵袭性真菌感染过程中发生肝毒性的因素。方法 采用HPLC测定伏立康唑谷浓度(ρmin),采用CTCAE标准评价患者使用伏立康唑后是否发生肝毒性,采用多元线性回归和分类回归树(CART)探讨影响肝毒性的因素。结果 本试验中共监测了144例患者的328个7血样,其中18例患者出现了肝毒性,伏立康唑在发生肝毒性患者中的ρmin显著高于未出现肝毒性患者的ρmin[(3.49±2.31) μg·mL-1 vs (1.96±1.48) μg·mL-1, P<0.05]。伏立康唑在不同年龄、性别、CYP2C19基因表型患者中的肝毒性发生率无显著差异。但CART结果表明,伏立康唑ρmin≤2.89 μg·mL-1的女性患者、伏立康唑ρmin>2.89 μg·mL-1的慢代谢患者及伏立康唑ρmin>2.89 μg·mL-1合并使用CYP2C19抑制剂的非慢代谢患者易出现肝毒性。结论 在侵袭性真菌感染患者中对伏立康唑ρmin和肝功进行监测,有利于提高伏立康唑治疗的安全性。

Abstract

OBJECTIVE To explore the factors that association with voriconazole-related hepatotoxicity in patients with invasive fungal infections. METHODS Voriconazole trough plasma concentrations(ρmin) were measured by high-performance liquid chromatography(HPLC). Voriconazole-related hepatotoxicity was defined according to Common Terminology Criteria for Adverse Events(CTCAE), and the multivariate linear regression and classification and regression tree(CART) were used to explore the factors that association with hepatotoxicity. RESULTS A total of 328 samples from 144 patients were measured, and 18 patients with signs of hepatotoxicity. There was a significant difference between the voriconazole ρmin in patients with hepatotoxicity and those without hepatotoxicity [(3.49±2.31) μg·mL-1 vs (1.96±1.48 )μg·mL-1, P<0.05]. There is no significant difference of hepatotoxicity in patients with different age, sex and CYP2C19 genetic status. However, CART revealed that hepatotoxicity was more likely to happen in the following populations:①female patients with voriconazole ρmin≤ 2.89 μg·mL-1; ②poor metabolizer with voriconazole ρmin>2.89 μg·mL-1; ③non-poor metabolizer with voriconazole ρmin>2.89 μg·mL-1who received CYP2C19 inhibitor. CONCLUSION Monitoring voriconazole ρmin and liver function could benefit to the safety of voriconazole therapy in patients with invasive fungal infections.

关键词

伏立康唑 / 肝毒性 / CYP2C19基因表型 / 分类回归树 / 治疗药物监测

Key words

voriconazole / hepatotoxicity / CYP2C19 genetic status / classification and regression tree / therapeutic drug monitoring

引用本文

导出引用
王陶陶, 陈思颖, 尤海生, 董海燕, 王雪, 董亚琳. 侵袭性真菌感染患者伏立康唑肝毒性的研究[J]. 中国药学杂志, 2018, 53(4): 290-294 https://doi.org/10.11669/cpj.2018.04.010
WANG Tao-tao, CHEN Si-ying, YOU Hai-sheng, DONG Hai-yan, WANG Xue, DONG Ya-lin. Hepatotoxicity Study of Voriconazole Therapy in Patients with Invasive Fungal Infections[J]. Chinese Pharmaceutical Journal, 2018, 53(4): 290-294 https://doi.org/10.11669/cpj.2018.04.010
中图分类号: R969   

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基金

国家自然科学基金资助项目(81703618)
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