Objective: To explore the application value of simultaneous monitoring of voriconazole (VRCZ) and voriconazole N-oxide (VNO) in efficacy and safety of VRCZ in the prevention and treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients before engraftment (i.e., days +1 to +30 after transplantation).
Methods: The influencing factors of VRCZ, VNO concentration and MR (CVNO/CVRCZ) and the difference of VRCZ in the prevention and treatment of fungal infection and liver and kidney injury were analyzed. The receiver operating characteristic curve (ROC) was used to analyze the differences (the corresponding to the maximum of the Youden index on the curve was set as the cut-off value) to confirm the critical value.
Results: The factors affecting VRCZ concentration (CVRCZ), VNO concentration (CVNO) and MR were patient weight, VRCZ daily dose, and transplantation type (all P < 0.05). CVRCZ and CVNO in the effective group were higher than those in the ineffective group (P < 0.001), the opposite of MR (P < 0.001); the liver and renal injury group had lower MR than the normal group (P < 0.05). ROC showed that CVRCZ, C VNO and MR had important value in predicting VRCZ in the prevention and treatment of invasive fungal infections in allo-HSCT patients before engraftment, and their cutoff of concentrations were 0.95 μg/ml, 1.35 μg/ml and 1.645, respectively (AUC: 0.9677, 0.7634, 0.9564). CVRCZ and MR can assist in indicating liver ［cutoff values: 0.65 μg/ml, 1.96 (AUC: 0.5971, 0.6663)］ and renal injury ［cutoff values: 0.95 μg/ml, 1.705 (AUC: 0.6039, 0.6164)］.
Conclusion: The great value of simultaneous monitoring of VRCZ, VNO and MR can predict in the efficacy and safety of VRCZ in allo-HSCT patients before engraftment. The prediction accuracy of CVRCZ was higher than that of MR, followed by that of CVNO. Increased CVRCZ and decreased MR increase the risk of liver and kidney injury.
题目: 伏立康唑及其代谢产物浓度监测在异基因造血干细胞移植患者中的应用研究.
目的: 探索移植后植入前（即移植后+1至+30 d）伏立康唑（voriconazole，VRCZ）及其代谢产物氮氧化物（voriconazole N-oxide，VNO）浓度监测在VRCZ用于异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation，allo-HSCT）患者防治真菌感染疗效和安全性中的应用价值。.
方法: 分析VRCZ、VNO浓度及MR（CVNO/CVRCZ）的影响因素及在VRCZ防治真菌感染和发生肝肾损伤中的差异，并采用受试者工作特征曲线（ROC）对其进行分析（将曲线上约登指数最大一点对应值设定为临界值），确证其临界值。.
结果: 影响VRCZ浓度（CVRCZ）、VNO浓度（CVNO）和MR的因素为：患者体重、VRCZ每日给药量及移植类型等（均P < 0.05）。有效组CVRCZ和CVNO均明显高于无效组（P < 0.001），MR则相反（P < 0.001）；肝、肾功能损伤组MR均明显低于正常组（P < 0.05）。ROC显示，CVRCZ、CVNO和MR预测allo-HSCT患者移植后植入前VRCZ防治侵袭性真菌感染的临界值分别为0.95 μg/ml、1.35 μg/ml、1.645（AUC分别为0.9677、0.7634、0.9564）。CVRCZ和MR可以辅助提示患者肝［其临界值分别为0.65 μg/ml、1.96（AUC分别为0.5971、0.6663）］、肾损伤［其临界值分别为0.95 μg/ml、1.705（AUC分别为0.6039、0.6164）］.
结论: 同时监测VRCZ、VNO浓度及MR对预测allo-HSCT患者移植后植入前VRCZ防治侵袭性真菌感染具有重要价值，CVRCZ 预测有效的准确性高于MR及C VNO；CVRCZ升高、MR降低会增加肝肾损伤的发生风险。.
Keywords: voriconazole; voriconazole N-oxide; allogeneic hematopoietic stem cell transplantation; therapeutic drug monitoring; safety.