重症患者复方磺胺甲(口恶)唑血药峰浓度与不良反应的相关性研究

目的:评估重症患者使用复方磺胺甲■唑发生的不良反应与血药峰浓度(C_max)的相关性及其毒性阈值。方法:采用回顾性研究的方法,收集2016年1月至2021年12月某三甲医院重症监护室使用复方磺胺甲■唑治疗并进行治疗药物监测的患者信息,使用Naranjo评分量表评价复方磺胺甲■唑与不良反应的关联性,并分析磺胺甲■唑及甲氧苄啶C_max与不良反应发生之间的相关性。结果:本研究共获得109人次磺胺甲■唑的浓度数据及87人次甲氧苄啶的浓度数据,未发现皮疹、恶心呕吐、肝毒性及肾毒性的发生与磺胺甲■唑及甲氧苄啶C_max有相关性(P>0.05),发生血液系统毒性及高钾血症的患者其甲氧苄啶C_max显著高于未发生的患者(P<0.05),进一步通过受试者工作特征曲线分析得到高钾血症的甲氧苄啶C_max最佳阈值为8.75μg·mL^-1。结论:有必要对使用复方磺胺甲■唑的重症患者进行治疗药物监测,甲氧苄啶C_max>8.75μg·mL^-1...

The relationships of peak plasma concentration with toxicity of trimethoprim-sulfamethoxazole in ICU patients

OBJECTIVE To evaluate the correlation between the adverse reactions of sulfamethoxazole(SMX)/trimethoprim(TMP)and the peak plasma concentration(C_max)and its toxicity threshold in critically ill patients.METHODS A retrospective analysis was conducted on patients who were continuously treated with SMX/TMP for severe infection and underwent therapeutic drug monitoring(TDM)in the intensive care unit of a tertiary hospital from January 2016 to December 2021.The occurrence of SMX/TMP-related adverse reactions was judged by Naranjo scale.The obtained adverse reactions data and the C_max of SMX/TMP were subjected to analysis of the correlation. RESULTS A total of 109 concentration data of SMX and 87 concentration data of TMP were respectively obtained in this study.The C_max of TMP in patients with hematological toxicity and hyperkalemia were significantly higher than that in patients without toxicity(P＜0.05),but no correlation was found between the occurrence of rash,nausea and vomiting,hepatotoxicity,nephrotoxicity and the C_max of SMX/TMP(P＞0.05).Further receiver operating characteristic analysis showed that the threshold of TMP peak concentration for hyperkalemia was C_max＞8.75 μg·mL^-1.CONCLUSION It is necessary to monitor the drug concentration of critical patients using SMX/TMP,which may increase the probability of hyperkalemia at C_max ＞8.75 μg·mL^-1.