血液病患者伏立康唑清除的影响因素及其不良反应

Factors Influencing and Adverse Reactions of Voriconazole Clearance in Patients with Hematological Diseases

目的:通过监测血液系统疾病患者伏立康唑谷浓度(C_(min)),评估血液病患者伏立康唑清除的影响因素及其不良反应,为伏立康唑的临床合理使用提供理论依据。方法:选取武汉市第一医院2018年5月至2019年12月给予伏立康唑预防及治疗的血液病患者136例,分析患者C-反应蛋白、白蛋白及肌酐与伏立康唑C_(min)的相关性,检测糖皮质激素处理后伏立康唑C_(min)水平的改变,并通过分层分析探究伏立康唑不良反应事件。结果:136例患者中,男性77例(56.62%),女性59例(43.38%)。患者伏立康唑C_(min)与C-反应蛋白水平和肌酐水平呈正相关性(r=0.277,r=0.208);而伏立康唑C_(min)与白蛋白水平呈负相关性(r=-2.673)。给予糖皮质激素治疗的患者伏立康唑C_(min)显著降低(P<0.05)。伏立康唑C_(min)分层分析发现,与C_(min)为1.0-5.0 mg/L组相比,伏立康唑C_(min)>5.0 mg/L组患者视觉障碍的发生率明显升高(χ^(2)=4.318,P=0.038)。结论:C-反应蛋白、白蛋白及肌酐水平与伏立康唑血药浓度密切相关,炎症及低营养状态可能抑制血液病患者伏立康唑的清除。有必要对使用伏立康唑的血液病患者进行血药浓度监测,并及时调整给药剂量,以减少不良反应。

Objective:To monitor the changes of voriconazole minimum concentration(C_(min))in patients with hematological diseases,and evaluate the factors influencing and adverse reactions of voriconazole clearance in patients with hematological diseases,so as to provide a theoretical basis for reasonable clinical use of voriconazole.Methods:136 patients with hematological diseases who used voriconazole in Wuhan NO.1 Hospital from May 2018 to December 2019 were selected.The correlation between C-reactive protein,albumin,creatinine and voriconazole C_(min) were analyzed,and the changes of voriconazole C_(min) after glucocorticoid treatment was also detected.In addition,stratified analysis was used to explore the adverse events of voriconazole.Results:Among 136 patients,77 were male(56.62%)and 59 were female(43.38%).There were positive correlations between voriconazole C_(min) and C-reactive protein and creatinine levels(r=0.277,r=0.208),while voriconazole C_(min) was negatively correlated with albumin level(r=-2.673).Voriconazole C_(min) in patients treated with glucocorticoid was decreased significantly(P<0.05).In addition,sratified analysis of voriconazole C_(min) showed that compared with voriconazole C_(min) 1.0-5.0 mg/L group,the incidence of adverse reactions of visual impairment in voriconazole C_(min)>5.0 mg/L group was increased(χ^(2)=4.318,P=0.038).Conclusion:The levels of C-reactive protein,albumin and creatinine are closely related to the voriconazole C_(min),which indicate that inflammation and hyponutrition may prevent the clearance of voriconazole in patients with hematological diseases.It is necessary to monitor the voriconazole C_(min) of patients with hematological diseases,and adjust the dosage in time to reduce adverse reactions.