多粘菌素用法及药代动力学研究进展  

Research Progress on Usage and Pharmacokinetics of Polymyxin

作　　者：李立[1] 叶璟[1] 胡蕾[1] 谈林华[1] LI Li;YE Jing;HU Lei;TAN Linhua(Department of Surgical Intensive Care Unit,Children's Hospital,Zhejiang University School of Medicine,Hangzhou,Zhejiang 310052,China)

机构地区：[1]浙江大学医学院附属儿童医院外科重症监护室、国家儿童健康与疾病临床医学研究中心,杭州310052

出　　处：《药学与临床研究》2021年第6期454-457,461,共5页Pharmaceutical and Clinical Research

基　　金：国家中心自主设计项目全国多中心临床研究项目(G20B0009)。

摘　　要：多粘菌素是一种阳离子多肽类抗生素,在1950年代首次用于临床,但在1970年代由于肾毒性和神经毒性而被基本弃用。最近,多重耐药革兰阴性病原体的流行,迫使多粘菌素再次成为临床治疗多重耐药革兰阴性菌的最后一线药物手段。临床证据表明,多粘菌素B由于以其活性形式给药,其药代动力学变异较小,主要通过非肾脏途径消除,因此肾功能损害患者无需调整用药剂量。而CMS可通过肾小球滤过和肾小管排泄迅速清除,20%~25%自发水解为粘菌素。但是不同患者具有其特殊的病理生理状态,药代动力学参数与健康志愿者间存在较大差异,按照健康人体的药代动力学参数指导用药,可能会导致药物剂量不足或剂量过大而增加毒副作用。Polymyxin,a polypeptide antibiotic,was first used clinically in the 1950s,but was largely abandoned in the 1970s due to nephrotoxicity and neurotoxicity.Recently,high prevalence of multidrug-resistance(MDR)gram-negative pathogens has forced clinicians to use colistin as the last-line therapy against these challenging infections again.Clinical evidence from healthy volunteers shows that polymyxin B,which is administered in its active form and primarily eliminated via non-renal pathways,has less variability in pharmacokinetics(PK).Therefore,there is no need to adjust the dosage in patients with renal impairment.Colistinmethanesulfonate(CMS)is rapidly removed by glomerular filtration and renal tubular excretion,and 20%-25%of CMS is spontaneously hydrolyzed to colistin.However,there are great differences in the pathophysiological state and PK parameters between the patients and the healthy volunteers,medication refering to the parameters of healthy people may lead to insufficient drug dose or increased side effects because of excessive drug dose.

关 键 词：多粘菌素 药代动力学 肾脏替代治疗 雾化吸入 

分 类 号：R969.1[医药卫生—药理学]