基于计算机模拟概述创新性软药瑞马唑仑  

Pharmacologic overview of the innovative soft drug remimazolam based on computer simulation

作　　者：管忍 董希玮[2] 马宁 张马忠[3] Guan Ren;Dong Xiwei;Ma Ning;Zhang Mazhong(Department of Anesthesiology,Changshu Hospital Affiliated to Soochow University,First People's Hospital of Changshu City,Changshu 215500,China;Department of Anesthesiology,First Affiliated Hospital,School of Medicine,Shihezi University,Shihezi 832008,China;Department of Anesthesiology&Pediatric Clinical Pharmacology Laboratory,Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)

机构地区：[1]苏州大学附属常熟医院,常熟市第一人民医院麻醉科,215500 [2]石河子大学医学院第一附属医院麻醉科,832008 [3]上海交通大学医学院附属上海儿童医学中心麻醉科,200127

出　　处：《国际麻醉学与复苏杂志》2020年第10期946-954,共9页International Journal of Anesthesiology and Resuscitation

基　　金：国家自然科学基金(81270414);上海市卫生与健康委员会重要薄弱学科建设项目(2015ZB0106)。

摘　　要：目的基于模拟和文献综述,概述新型超短效苯二氮类镇静/麻醉药瑞马唑仑的药理学特点、临床应用趋势和使用注意事项。方法以主题词"remimazolam"并关联"CNS7056""CNS7054"在PubMed数据库中进行文献检索,搜索描述咪达唑仑、丙泊酚和瑞芬太尼的药代学和药效学文献,提取药物药代学、药效学特征。模拟瑞马唑仑静脉注射、静脉输注、靶控输注(target controlled infusion,TCI)后药物浓度变化和药效学,包括起效时间、峰效应时间、维持时间、稳态浓度时间、稳态输注时间敏感性半衰期(context-sensitive half-times,CSHT)等。综述瑞马唑仑临床相关特点。结果静脉注射时,瑞马唑仑起效时间(1.2~2.9 min)较丙泊酚(0.8 min)慢,峰效应时间和维持时间两者相近且均远低于咪达唑仑;静脉输注期间,瑞马唑仑起效快于丙泊酚和咪达唑仑,三者达稳态浓度时间均较长;瑞马唑仑TCI时与静脉注射有相似的起效时间。瑞马唑仑和丙泊酚达稳态浓度时间相似,比咪达唑仑快、较瑞芬太尼慢。为获得相同目标浓度,瑞马唑仑的TCI给药速度/静脉输注速度比趋近1耗时>1 h,劣于瑞芬太尼而优于丙泊酚。瑞马唑仑CSHT相对恒定而丙泊酚CSHT随稳态输注时间延长逐渐增加,输注12 h后两者CSHT分别为5.9 min和13.9 min。结论瑞马唑仑不宜常规用作术前药或用于极短时间诊疗操作;用于麻醉诱导和维持时药理学特点与丙泊酚相似,停药后恢复稍好于丙泊酚,两者均适用TCI模式给药;瑞马唑仑用于ICU镇静具有良好的前景。瑞马唑仑临床应用尚需进一步探索,尤其是临床情况下的药物相互作用和特殊人群的使用。Objective To review the pharmacological characteristics,potential clinical applications and precautions based on the simulation and literature review.Methods PubMed was systematically searched for published articles in English to identify the studies of remimazolam or CNS7056 and CNS7054 including pre-clinical,clinical trial and clinical application.The pharmacokinetic and/or pharmacodynamic literatures describing midazolam,propofol and remifentanil were also searched,and characteristic parameters were extracted.The drug concentration changes and pharmacodynamics were simulated after intravenous bolus injection,intravenous infusion,and target-controlled infusion(TCI)of remimazolam,including onset time,peak effect time and maintenance time,steady-state effect time,the context-sensitive half-times(CSHT)after steady-state infusion,etc.The clinical characteristics of rimazolum were reviewed.Results The onset time of remimazolam(1.2-2.9 min)was slower than that of propofol(0.8 min)after bolus administration,both had similar peak effect time and maintenance time,which were much shorter than midazolam.During intravenous infusion,the onset time of remimazolam was faster than those of propofol and midazolam,and the three took a long time to reach steady state effect.TCI had a similar onset time as intravenous bolus injection.The time to reach steady-state effect time was similar for remimazolam and propofol,which were faster than midazolam and slower than remifentanil.With the same target plasma concentration,the ratio of TCI rate/continuous infusion rate of remimazolam approaching to unity took more than 1 h,which was inferior to remifentanil and better than propofol and midazolam.The CSHT of remimazolam was relatively constant while propofol increased gradually with steady-state infusion time.The CSHTs of the two were 5.9 min and 13.9 min after 12 h of steady-state infusion,respectively.Conclusions Remimazolam is not suitable for routine use as premedication or for extremely short procedural sedation/anesthesia.Remimazo

关 键 词：瑞马唑仑 药代学 药效学 计算机模拟 临床应用 静脉麻醉药 

分 类 号：TP391.9[自动化与计算机技术—计算机应用技术] R96[自动化与计算机技术—计算机科学与技术]