肾功能亢进对替考拉宁高剂量治疗方案下患者血药谷浓度的影响  

Effects of Augmented Renal Clearance on Blood Trough Concentration of Patients Receiving High-dose Regimen of Teicoplanin

作　　者：唐莲[1] 石璐 薛宏志 庄智伟[2] 袁云龙 钱春霞 朱金伟 许晓文 朱亚松 刘纪松 沈奕[2] 陆件[2] TANG Lian;SHI Lu;XUE Hongzhi;ZHUANG Zhiwei;YUAN Yunlong;QIAN Chunxia;ZHU Jinwei;XU Xiaowen;ZHU Yasong;LIU Jisong;SHEN Yi;LU Jian(Dept.of Pharmacy,the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital,Jiangsu Suzhou 215002,China;Intensive Care Unit,the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital,Jiangsu Suzhou 215002,China;Medical Laboratory,the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital,Jiangsu Suzhou 215002,China;College of Pharmacy,Xuzhou Medical University,Jiangsu Xuzhou 221004,China;Medical Laboratory of Hangzhou Baichen,Hangzhou 310000,China)

机构地区：[1]南京医科大学附属苏州医院/苏州市立医院药学部,江苏苏州215002 [2]南京医科大学附属苏州医院/苏州市立医院重症医学科,江苏苏州215002 [3]南京医科大学附属苏州医院/苏州市立医院医学检验科,江苏苏州215002 [4]徐州医科大学药学院,江苏徐州221004 [5]杭州佰辰医学检验所,杭州310000

出　　处：《中国药房》2020年第21期2650-2655,共6页China Pharmacy

基　　金：江苏省药学会天晴医院药学基金项目(No.Q2019071);苏州市2019年度科技发展计划(民生科技-医疗卫生应用基础研究[第三批])项目(No.SYSD2019186)。

摘　　要：目的:研究肾功能亢进(ARC)对替考拉宁高剂量给药方案下患者血药谷浓度的影响。方法:前瞻性收集2018年7月至2020年6月南京医科大学附属苏州医院/苏州市立医院重症监护室中目标性治疗使用替考拉宁高剂量方案的患者,根据矫正肌酐清除率分为ARC组和肾功能正常组。两组患者的替考拉宁给药方案均为负荷剂量600 mg,q12 h×3剂,维持剂量6~10 mg/kg,qd,并结合肌酐清除率及血药谷浓度调整给药剂量。采用高效液相色谱法测定两组患者在替考拉宁第4剂给药前30 min和第8~10剂给药前30 min的血药谷浓度,对比两组患者替考拉宁血药谷浓度、临床有效率、革兰氏阳性菌清除率及不良反应发生情况。结果:共纳入56例患者,18例纳入ARC组、38例纳入肾功能正常组。ARC组患者较肾功能正常组患者更年轻(P<0.001),血清白蛋白水平更低(P=0.025)。ARC组患者第4剂给药前和第8~10剂给药前血药谷浓度均低于肾功能正常组(P=0.034;P=0.035)。ARC组和肾功能正常组患者的第8~10剂给药前血药谷浓度均高于同组第4剂给药前血药谷浓度(P=0.003;P<0.001)。ARC组临床有效率为77.8%、革兰氏阳性菌清除率为76.2%,均较肾功能正常组低,但差异无统计学意义(P=0.195;P=0.223)。两组患者均未出现肝功能损害、血细胞减少、过敏反应等情况,但肾功能正常组有1例患者的急性肾损害与替考拉宁用药的因果关系被评定为"很可能"。结论:ARC患者更年轻、多数存在低蛋白血症,其在替考拉宁高剂量治疗方案下的血药谷浓度较肾功能正常者显著降低。建议对危重症感染的ARC患者宜加大替考拉宁负荷剂量以使其血药谷浓度快速达标。OBJECTIVE:To study the effects of augmented renal clearance(ARC)on blood trough concentration of patients receiving high-dose regimen of teicoplanin.METHODS:Patients who received high-dose regimen of teicoplanin in the ICU were prospectively collected from the Affiliated Suzhou Hospital of Nanjing Medical University/Suzhou Municipal Hospital during Jul.2018-Jun.2020.They were divided into ARC group and normal renal function group according to corrected creatinine clearance.The dosage regimen of teicoplanin in the two groups were loading dose of 600 mg,q12 h×3 doses,maintenance dose of 6-10 mg/kg,qd,and the dosage was adjusted in combination with creatinine clearance rate and blood trough concentration.The trough concentration of blood samples which were collected 30 min before the 4th and 8th-10th dosage of teicoplanin were determined by HPLC.Trough concentration,clinical efficacy,Gram-positive bacterial clearance rate and the occurrence of ADR were compared between 2 groups.RESULTS:A total of 56 patients were included and divided into ARC group(18 cases)and normal renal function group(38 cases).ARC group had younger age(P<0.001)and lower serum albumin level(P=0.025)than normal renal function group.The trough concentrations before administration of the 4 th and 8 th-10 th dosage in ARC group were lower than normal renal function group(P=0.034;P=0.035).The trough concentrations in the ARC group and normal renal function group before 8 th-10 th dosage were all higher than 30 min before the 4 th dosage(P=0.003;P<0.001).The clinical efficacy rate and the clearance rate of Gram-positive bacteria in ARC group were 77.8%and 76.2%,which were lower than those of the normal renal function group,but there was no statistical difference(P=0.195;P=0.223).There was no liver function damage,hemocytopenia and allergic reaction in both groups,but in the normal renal function group,the causal relationship between acute renal damage and teicoplanin was assessed as"very likely"in one patient.CONCLUSIONS:ARC patients are younger,most

关 键 词：肾功能亢进 替考拉宁 高剂量 血药谷浓度 临床疗效 

分 类 号：R978.1[医药卫生—药品]