This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R² = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

中文翻译：

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Child-Pugh C 级肝硬化患者伏立康唑谷浓度的预测因素：一项前瞻性研究

这项前瞻性观察性研究旨在临床描述 Child-Pugh C 级患者的伏立康唑给药和谷浓度，并调查谷浓度的变异性。对来自 43 名 Child-Pugh C 级患者的总共 144 个伏立康唑谷浓度进行了分析。大多数患者 (62.8%) 接受了调整。重复测量的谷浓度一般高于第一次和最后一次（中值，4.33 vs. 2.99，3.90 mg/L）。八名具有理想初始浓度的患者后来在没有调整每日剂量的情况下获得了超治疗，这意味着蓄积。按日剂量计算，六组之间的浓度有显着差异（p= 0.006）。双变量相关分析显示，性别、CYP2C19基因分型、日剂量、凝血酶原时间活性、国际标准化比值、血小板和终末期肝病模型评分是浓度的显着影响因素。随后，上述前四个因素进入逐步多元线性回归模型（方差膨胀因子<5），表明CYP2C19检测对Child-Pugh C级肝硬化患者的精准医疗有意义。该方程拟合良好并解释了 34.8% 的浓度变化 (R ²= 0.348）。总之，由于药物标签中没有对 Child-Pugh C 级患者的推荐，因此临床上需要更加谨慎地给药。给药方案的调整应主要根据反复治疗药物监测的结果。