利奈唑胺在儿童体内暴露量与血小板减少症发生风险的关系研究

Correlation between exposure of linezolid to children and risk of thrombocytopenia

  • 摘要: 目的 考察儿童群体中利奈唑胺的体内暴露量与血小板减少症发生风险之间的关系。方法 选取武汉儿童医院2015年6月-2018年5月使用利奈唑胺进行抗感染治疗的108名患儿为研究对象,观察利奈唑胺相关血小板减少症的发生率并测定利奈唑胺暴露量参数:谷浓度(Cmin)、峰浓度(Cmax)和24 h内稳态血药浓度时间曲线下的面积(AUC0~24h)。采用受试者工作特征(ROC)曲线考察利奈唑胺暴露量与血小板减少症之间的关系,应用Logistic回归模型对不同暴露量水平下血小板减少症的发生概率进行评估。结果 本研究中有24名患儿(22.2%)发生利奈唑胺相关血小板减少症。AUC0~24h与血小板减少症之间的关联性最强,其ROC曲线下面积为0.857,最佳切点值为387.6 mg/h/L。当AUC0~24h大于该值时血小板减少症发生风险较高。结论 利奈唑胺暴露量与血小板减少症密切相关,AUC0~24h是预测利奈唑胺相关血小板减少症发生风险的最佳暴露量参数,临床可根据该参数及时调整给药方案以避免严重不良反应的发生。

     

    Abstract: OBJECTIVE To observe the correlation between the exposure of linezolid to children and the risk of thrombocytopenia. METHODS A total of 108 children who were given linezolid for treatment of infection in Wuhan Children’s Hospital from Jun 2015 to May 2018 were enrolled in the study. The incidence of linezolid-related thrombocytopenia was observed, the parameters of exposure of linezolid such as trough concentration (Cmin), peak concentration (Cmax)and area under the plasma concentration-time curve from time zero to 24 hours (AUC0~24h) were determined. The correlation between the exposure of linezolid and the thrombocytopenia was observed by means of receiver-operating-characteristic (ROC) curve, and the probability of incidence of thrombocytopenia was evaluated under different exposure levels by using logistic regression model. RESULTS Totally 24 (22.2%) children had linezolid-related thrombocytopenia. AUC0~24h was closely associated with the thrombocytopenia, the area under ROC curve was 0.857, and the optimal cutoff value was 387.6 mg/h/L. The children were at high risk of thrombocytopenia when the AUC0~24h was greater than 387.6 mg/h/L. CONCLUSION The exposure of linezolid is closely associated with the thrombocytopenia, AUC0~24h is the optimal exposure parameter for prediction of the linezolid-related thrombocytopenia, and it is necessary for the hospital to adjust the dosing regimens based on the parameter so as to prevent severe adverse reactions.

     

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