Abstract��OBJECTIVE To explore the factors that association with voriconazole-related hepatotoxicity in patients with invasive fungal infections. METHODS Voriconazole trough plasma concentrations(��min) 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 ��min in patients with hepatotoxicity and those without hepatotoxicity [(3.49��2.31) ��g��mL-1 vs (1.96��1.48 )��g��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:��female patients with voriconazole ��min�� 2.89 ��g��mL-1; ��poor metabolizer with voriconazole ��min>2.89 ��g��mL-1; ��non-poor metabolizer with voriconazole ��min>2.89 ��g��mL-1who received CYP2C19 inhibitor. CONCLUSION Monitoring voriconazole ��min and liver function could benefit to the safety of voriconazole therapy in patients with invasive fungal infections.
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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. Chinese Pharmaceutical Journal, 2018, 53(4): 290-294.
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