Therapeutic drug monitoring and safety evaluation of voriconazole in the treatment of pulmonary fungal diseases

作者：Kunlu Shen, Yu Gu, Yu Wang, Yajie Lu, Yueyan Ni, Huanhiuan Zhong, Yi Shi, Xin Su · 发表于：Therapeutic Advances in Drug Safety · 年份：2022 · DOI：10.1177/20420986221127503 · 被引用次数：33 · 研究领域：Antifungal resistance and susceptibility、Cholinesterase and Neurodegenerative Diseases、Fungal Infections and Studies

Aims: The gene polymorphism of voriconazole metabolism–related liver enzyme is notable in East Asia population. It casts a significant influence on the rational use of voriconazole. We conducted this study to investigate the relationship between steady-state voriconazole trough concentration (C trough ) and adverse effects (AEs), especially hepatotoxicity. Methods: We conducted a real-world study in the Jinling Hospital from January 2015 to June 2020. A total of 140 patients receiving voriconazole were enrolled in this study. The determination and scoring of voriconazole-associated hepatotoxicity were performed according to the Roussel Uclaf Causality Assessment Method scoring scale and the severity of hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE). Results: Elevated steady-state voriconazole C trough with concomitant AEs are the most common reason for dose adjustments during treatment. Compared with the group without any AEs, voriconazole C trough was significantly higher in the hepatotoxicity and neurotoxicity groups, and the incidence of both events showed an overall increasing trend with increasing voriconazole C trough. Hepatotoxicity occurred in 66.7% of patients within 7 days of the first dose of voriconazole and 94.4% within 15 days of the dose. Steady-state voriconazole C trough >3.61 mg/l was associated with an increased incidence of hepatotoxicity (area under the curve = 0.645, p = 0.047). Logistic regression an...