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Population pharmacokinetics of rocuronium delivered by target-controlled infusion in adult patients

Chinese Medical Journal 2010年第18期123卷 2543-2547页

作者： yang lu WANG Hui-{2.ng zhang {2.-ping bi shan-shan lu wei yang {12.-xian GUO xiang-yang department of anesthesiology Peking University Third Hospital Beijing 100191 China Peking university School of Pharmaceutical Sciences Beijing 100191 China department of anesthesiology Peking University People's Hospital Beijing 100034 China

background Target-controlled infusion （TCI） has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model （NONMEM）, and to investigate the influence of relevant factors in adult patients. Methods Fourteen ASA Ⅰ-Ⅱ patients undergoing elective laparoscopy operation with general anesthesia were included. After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration （Cpt） was 2.0 μg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90%-95%. TCI rocuronium was stopped 30 minutes before the end of the operation. Arterial blood was drawn before anesthesia at 0, 2. 4, 6, 8, 10, 15, 2., 30, 45, 60, 12., 180, 2.0 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry （LC-MS/MS）. The population pharmacokinetics analysis was performed using NONMEM program. Results The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-comparment model. Pharmacokintic parameters were clearance （CL）1=0.2.5 L/min, CL2.0.32. L/min, CL3=0.02.2.L/min, volumes of distribution （V）1=4.00 L, V2.2.2. L, V3=4.2. L, Vdss=10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight. Conclusions No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters.

关键词： anesthesia rocuronium pharmacokinetics mass spectrometry

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Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2.Omicron strain infection in china:A national multicenter survey of 35,566 individuals

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 113-120页

作者： Meng-Fan liu Rui-Xia Ma xian-{2.o Cao Hua zhang Shui-Hong Zhou wei-Hong Jiang Yan Jiang Jing-Wu Sun Qin-Tai yang Xue-Zhong li Ya-Nan Sun li Shi Min Wang Xi-Cheng Song Fu-Quan Chen Xiao-Shu zhang Hong-Quan wei Shao-Qing Yu Dong-Dong Zhu luo {2. Zhi-wei Cao Xu-ping Xiao Xin wei Zhi-Hong lin Feng-Hong Chen Chun-Guang shan Guang-Ke Wang Jing Ye Shen-Hong Qu Chang-Qing Zhao Zhen-lin Wang Hua-bin li Feng liu Xiao-Bo Cui Sheng-Nan Ye Zheng liu Yu Xu Xiao Cai wei Huang Ru-Xin zhang Yu-lin Zhao Guo-Dong Yu Guang-Gang Shi Mei-ping lu yang Shen Yu-Tong Zhao Jia-Hong Pei Shao-bing Xie Long-Gang Yu Ye-Hai liu Shao-wei Gu Yu-Cheng yang Lei Cheng Jian-Feng liu Graduate School of beijing university of Chinese Medicine BeijingChina department of Otorhinolaryngology Head and Neck Surgery China-Japan Friendship HospitalBeijingChina department of Otorhinolaryngology Head and Neck Surgery The First People's Hospital of YinchuanYinchuanChina department of Otorhinolaryngology The First People's Hospital of Yunnan ProvinceKunmingChina department of Otorhinolaryngology The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiChina department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouChina department of Otorhinolaryngology Head and Neck Surgery Xiangya Hospital Central South UniversityChangshaChina department of Otorhinolaryngology Head and Neck Surgery The Affiliated Hospital of Qingdao UniversityQingdaoChina department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of USTCHefeiChina department of Otorhinolaryngology Head and Neck Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina department of Otorhinolaryngology Head and Neck Surgery Qilu Hospital of Shandong UniversityJinanChina department of Otorhinolaryngology Head and Neck Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbinChina department of Otolaryngology The Second Hospital of Shandong UniversityShandong UniversityJinanChina department of Otorhinolaryngology Head and Neck Surgery Peking University People's HospitalBeijingChina department of Otorhinolaryngology Head and Neck Surgery Yantai Yuhuangding HospitalQingdao UniversityYantaiChina department of Otorhinolaryngology Head and Neck Surgery Xijing HospitalThe Fourth Military Medical UniversityXi'anChina Gansu Provincial Center for Disease Control and Prevention LanzhouChina department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of China Medical UniversityShenyangChina department of Otorhinolaryngology Head and Neck Surgery Tongji Hospit

Objective:This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in ***:This study was conducted by 45 tertiary Grade-A hospitals in *** and offline questionnaire data were obtained from patients infected with COVID-19 between December 2.,2.2.,and February 2.,*** collected information inc{2.ded basic demographics,medical history,smoking and drinking history,vaccination history,changes in olfactory and gustatory functions before and after infection,and other postinfection symptoms,as well as the duration and improvement status of olfactory and gustatory ***:Complete questionnaires were obtained from 35,566 *** overall incidence of olfactory and taste dysfunction was 67.75%.Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste *** received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such *** infection,the average olfactory and taste VAS scores were 8.41 and 8.51,respectively;after infection,they decreased to 3.69 and 4.2. and recovered to 5.83 and 6.55 by the time of the *** median duration of dysosmia and dysgeusia was 15 and 12.days,respectively,with 0.5%of patients having symptoms lasting for more than 2. *** overall self-reported improvement rate was 59.16%.Recovery was higher in males,never smokers,those who received two or three vaccine doses,and those that had never experienced dental health issues,or chronic accompanying ***:The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2.virus is high in *** and prognosis are inf{2.enced by several factors,inc{2.ding sex,SARS-CoV-2.vaccination,history of head-facial trauma,nasal and oral health status,smoking and drinking history,and the persistence of accompanying symptoms.

关键词： epidemiologic studies incidence olfactory disorders prognosis SARS-CoV-2 taste disorders

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Original article Population pharmacokinetics of remifentanil in patients undergoing orthotopic liver transplantation

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Chinese Medical Journal 2009年第9期122卷 1032-1038页

作者： zhang li-{2. yang lu bi shan-shan lu wei zhang xian-hua ZHAI Suo-di DUAN li-{2. department of anesthesiology Peking {2. third hospital Beijing 100191--China department of Pharmacy Peking university {2. Beijing 100191 China department of Gastroenterology Peking university {2. Be~jing 100191--China School of Pharmaceutical Sciences Peking University Beijing100191 China

backgroud little is known about the inf{2.ence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the diffe... 详细信息

backgroud little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation （OLT） and the influence of relevant factors.Methods Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 IJg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 （baseline）, 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry （HPLC/MS/MS）. Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling （NONMEM）.Results The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment （V1） and the volume of distribution in the peripheral compartment （V2） were influenced by body weight.Conclusions The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V1 and V2.

关键词： remifentanil liver transplantation pharmacokinetics anesthesia

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药物动力学/药效动力学在研究药物相互作用中的应用─反应曲面模型法研究瑞芬太尼与七氟醚联合应用(英文)

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中国临床药理学与治疗学 2007年第10期12卷 1151-1156页

作者： yang lu yang ba-xian zhang li-ping bi shan-shan lu {12. department of anesthesiology Third Hospital Peking University Beijing 100083 China department of anesthesiology People＇s Hospital Peking University Beijing 100083 China Deptartment of Pharmaceutics School of Pharmaceutical Science Peking University Beijing 100083 China State Key Lab. of Natural and biomimetic Drugs Beijing 100083 China

目的:全麻中两种以上的药物合并应用比单一麻醉剂更为有效。本研究是为确定中国成年患者全麻期间合并应用七氟醚与瑞芬太尼时药物相互作用的方式,并以反应曲面模型法对其进行表述。方法:1.试验设计:研究采用平行实验设计,65例病人(ASAI... 详细信息

目的:全麻中两种以上的药物合并应用比单一麻醉剂更为有效。本研究是为确定中国成年患者全麻期间合并应用七氟醚与瑞芬太尼时药物相互作用的方式,并以反应曲面模型法对其进行表述。方法:1.试验设计:研究采用平行实验设计,65例病人(ASAI级,各项指标正常,无长期服用阿片类药物史)入选本次试验,随机选定并维持一定的呼末七氟醚浓度[≤2.AC(0.3 %-3.4 %)] ,逐渐增加靶控输注的瑞芬太尼浓度(≤10 ng/mL) ,观察不同浓度组合时患者对喉镜置入刺激的反应以确定麻醉是否完全。2.反应曲面模型法进行药物动力学/药效动力学分析:两药合用的效果通过对喉镜置入时的反应进行评估,0和1分别代表有或没有体动反应。以下面的药效学模型表述体动反应消失的概率(P)其中Us ,Ur分别为标准化的七氟醚与瑞芬太尼水平;U50为达最大效应一半时的药物综合标准化水平;r为形状因子;I(Q)为药物相互作用的强度函数。模型通过作图、目标函数改变以及参数的生理/临床学的合理性等几方面进行评价。P=[U50/I((QU)s]+r+U(r)Urs+Ur)r结果与结论:研究表明瑞芬太尼与七氟醚合用时为协同式相互作用,上述反应曲面模型与实际观测值有较好的拟合。应用NONMEM得到喉镜置入刺激时的参数(RSE%)为U50=6.62.10.6) ,C50 ,sevo=1.71 %(12.9) ,C50 ,remi=12.4 ng/mL(19.0) ,Imax=2.31 ,Qmax=0.706。所得数值的加权残差均小于3。结果表明与传统方法相比,反应曲面模型法可以得到较好的拟合质量,为药物相互作用的研究提供了一种新颖思路和有效手段。

关键词：药物相互作用体动反应瑞芬太尼药效动力学药物动力学七氟醚模型法曲面

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药物动力学/药效动力学在研究药物相互作用中的应用—反应曲面模型法研究瑞芬太尼与七氟醚联合应用(英文)

药物动力学/药效动力学在研究药物相互作用中的应用—反应曲面模...

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中国药理学会临床药理学专业委员会会议暨第十次全国临床药理学学术会议

作者： yang lu~1 yang ba-xian~2.zhang li-ping~1 bi shan-shan~3 lu wei~(3,4) 1 department of anesthesiology,third hospital,Peking university,beijing 100083,china 2 department of anesthesiology,People’s hospital,Peking university,beijing 100083,china 3 Deptartment of Pharmaceutics,School of Pharmaceutical Science,Peking university,beijing 100083,china 4 State Key Lab.of Natural and biomimetic Drugs,beijing 100083,china

目的：全麻中两种以上的药物合并应用比单一麻醉剂更为有效。本研究是为确定中国成年患者全麻期间合并应用七氟醚与瑞芬太尼时药物相互作用的方式,并以反应曲面模型法对其进行表述。方法：1．试验设计：研究采用平行实验设计,65例病人(A... 详细信息

目的：全麻中两种以上的药物合并应用比单一麻醉剂更为有效。本研究是为确定中国成年患者全麻期间合并应用七氟醚与瑞芬太尼时药物相互作用的方式,并以反应曲面模型法对其进行表述。方法：1．试验设计：研究采用平行实验设计,65例病人(ASA Ⅰ级,各项指标正常,无长期服用阿片类药物史)入选本次试验,随机选定并维持一定的呼末七氟醚浓度[≤2.AC(0．3％-3．4％)],逐渐增加靶控输注的瑞芬太尼浓度(≤10 ng/mL),观察不同浓度组合时患者对喉镜置入刺激的反应以确定麻醉是否完全。2.反应曲面模型法进行药物动力学/药效动力学分析：两药合用的效果通过对喉镜置入时的反应进行评估,0和1分别代表有或没有体动反应。以下面的药效学模型表述体动反应消失的概率(P) 其中 Us,Ur 分别为标准化的七氟醚与瑞芬太尼水平;U为达最大效应一半时的药物综合标准化水平;r 为形状因子;I(Q)为药物相互作用的强度函数。模型通过作图、目标函数改变以及参数的生理/ 临床学的合理性等几方面进行评价。 p=((Us+Ur))/([U/I(Q)]+(Us+Ur)) 结果与结论：研究表明瑞芬太尼与七氟醚合用时为协同式相互作用,上述反应曲面模型与实际观测值有较好的拟合。应用 NONMEM 得到喉镜置入刺激时的参数(RSE%)为 U=6．62.10．6),C= 1．71%(12.9),C=12.4 ng/mL(19．0),I= 2.31,Q=0．706。所得数值的加权残差均小于3。结果表明与传统方法相比,反应曲面模型法可以得到较好的拟合质量,为药物相互作用的研究提供了一种新颖思路和有效手段。

关键词： drug-drug interactions synergy response-surface

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遗传性耳聋基因治疗临床指南

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实用医院临床杂志 2024年第2期21卷 39-44页

作者：齐洁玉谈方志张李燕陆玲王洪阳李文妍刘闻闻付小龙贺祖宏丁小琼孙珊方巧军董耀东朱学伟童步升曹现宝郭敏范欣淼汪芹马璐张天虹于亚峰李永新樊建刚崔勇吴佩娜张宏征唐杰郭维维查定军叶放蕾何双八曹卫杨见明钱晓云赵宇孙敬武陈晓巍孙宇夏明王秋菊袁慧军冯永孔维佳杨仕明王海波高下李华伟徐磊柴人杰东南大学数字医学工程全国重点实验室附属中大医院耳鼻咽喉头颈外科生命科学与技术学院生命与健康高等研究院江苏省生物医学高新技术研究重点实验室江苏南京210096 南通大学神经再生联合创新中心江苏南通226001 北京理工大学航天中心医院神经内科生命学院北京10081 南京大学医学院附属鼓楼医院耳鼻喉头颈外科江苏省医学重点学科(实验室)江苏南京210008 中国人民解放军总医院耳鼻咽喉头颈外科医学部北京100853 听觉与平衡觉全国重点实验室北京100853 国家耳鼻咽喉疾病临床医学研究中心北京100853 聋病教育部重点实验室北京100853 聋病防治北京市重点实验室北京100853 复旦大学附属眼耳鼻喉科医院医学神经生物学国家重点实验室教育部脑科学前沿研究中心上海200031 复旦大学生物医学研究所上海200032 国家卫健委听觉医学重点实验室上海200031 复旦大学脑科学研究院和脑科学协同创新中心上海200032 山东大学山东省耳鼻喉医院耳鼻咽喉头颈外科山东济南250022 山东省耳鼻喉研究所山东济南250022 山东第一医科大学/山东省医学科学院医学科技创新中心山东济南250000 武汉大学中南医院耳鼻咽喉头颈外科湖北武汉430071 东南大学附属中大医院耳鼻咽喉头颈外科江苏南京210009 复旦大学附属眼耳鼻喉科医院耳鼻喉科上海200032 安徽医科大学第二附属医院耳鼻咽喉头颈外科安徽合肥230601 中国医科大学附属盛京医院耳鼻咽喉头颈外科辽宁沈阳110004 吉林大学中日联谊医院耳鼻咽喉头颈外科吉林长春130033 安徽医科大学第一附属医院耳鼻咽喉头颈外科安徽合肥230022 云南省第一人民医院耳鼻喉科云南昆明650032 昆明医科大学第一附属医院耳鼻喉科云南昆明650032 中国医学科学院北京协和医学院北京协和医院耳鼻咽喉科北京100730 中南大学湘雅二医院耳鼻咽喉头颈外科湖南长沙410008 南华大学衡阳医学院基础医学院细胞生物学与遗传学教研室细胞应激生物学衡阳市重点实验室湖南衡阳421001 哈尔滨医科大学附属第一医院黑龙江哈尔滨150001 苏州大学附属第一医院耳鼻咽喉科江苏苏州215006 首都医科大学附属北京同仁医院耳鼻咽喉头颈外科北京100730 四川省医学科学院·四川省人民医院/电子科技大学附属医院耳鼻咽喉头颈外科四川成都610072 广东省人民医院耳鼻咽喉头颈外科/广东省医学科学院/南方医科大学广东广州510080 南方医科大学珠江医院耳鼻咽喉头颈外科广东广州510282 空军军医大学西京医院耳鼻咽喉-头颈外科陕西西安710032 郑州大学第一附属医院耳科河南郑州450000 东南大学医学院附属南京同仁医院耳鼻咽喉头颈外科江苏南京211102 四川大学华西医院耳鼻咽喉头颈外科四川成都610041 中国科学技术大学附属第一医院耳鼻咽喉头颈外科安徽合肥230001 华中科技大学同济医学院附属协和医院耳鼻咽喉头颈外科湖北武汉430022 山东第一医科大学附属山东省立医院耳鼻咽喉科山东济南250021 山东省医学科学院医学科技创新中心山东济南250021 山东大学附属山东省立医院耳鼻咽喉科山东济南250021 国家卫生健康委耳鼻咽喉重点实验室山东济南250021 四川大学华西医院罕见病研究院四川成都6010041 南华大学衡阳医学院南华大学附属妇幼保健院湖南长沙410008 中南大学湘雅医院耳鼻咽喉头颈外科湖南长沙410008 上海人工耳蜗工程技术研究中心上海200031 东南大学深圳研究院广东深圳518063

遗传性耳聋是一种常见的遗传性疾病,新生儿的发病率为1‰~3‰。患者终身携带致病突变,导致不可逆性耳聋,至今尚无临床可用的治疗药物。在部分遗传性耳聋动物模型中,基因治疗已被证实为潜在有效的治疗方法。国内外已开展了多项遗传性耳... 详细信息

遗传性耳聋是一种常见的遗传性疾病,新生儿的发病率为1‰~3‰。患者终身携带致病突变,导致不可逆性耳聋,至今尚无临床可用的治疗药物。在部分遗传性耳聋动物模型中,基因治疗已被证实为潜在有效的治疗方法。国内外已开展了多项遗传性耳聋基因治疗的临床试验。其中,由东南大学附属中大医院牵头,联合国内多家医院成功开展的遗传性耳聋基因治疗临床试验,取得了显著的疗效,并积累了丰富的经验。为规范遗传性耳聋基因治疗并提供临床研究指导,全国多家医院的耳科专家讨论制定了遗传性耳聋基因治疗临床指南,内容涵盖了伦理审查、遗传性耳聋的诊断和入组标准、临床前准备、药物、疗效与安全性评估标准、术后言语康复等。本指南将为耳聋基因治疗的临床诊疗提供规范的理论和技术指导。

关键词：遗传性耳聋基因治疗临床指南

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