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Dose selection of chloroquine phosphate for treatment of COVID-19 based on a physiologically based pharmacokinetic model

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Acta Pharmaceutica Sinica B 2020年第7期10卷 1216-1227页

作者： Cheng Cui Miao Zhang xueting yao Siqi Tu Zhe Hou Valerie Sia Jie En Xiaoqiang Xiang Jing Lin Ting Cai Ning Shen Chunli Song Jie Qiao Shun Zhang Haiyan Li Dongyang Liu Drug Clinical Trial Center Peking University Third HospitalBeijing 100191China Department of Clinical Pharmacy School of PharmacyFudan UniversityShanghai 201203China Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province HwaMei HospitalUniversity of Chinese Academy of Sciences(Ningbo No.2 Hospital)Ningbo 315010China Department of Respirator Peking University Third HospitalBeijing 100191China Department of Orthopedics Peking University Third HospitalBeijing 100191China Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalBeijing 100191China

Chloroquine(CQ)phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019(COVID-19).To develop a physiologically-based pharmacokinetic(PBPK)model for predicting tissue distribution of CQ and apply it to optimize dosage regimens,a PBPK model,with parameterization of drug distribution extrapolated from animal data,was developed to predict human tissue distribution of *** physiological characteristics of time-dependent accumulation was mimicked through an active transport *** dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response *** model was also validated by clinical data from Chinese patients with *** novel PBPK model allows indepth description of the pharmacokinetics of CQ in several key organs(lung,heart,liver,and kidney),and was applied to design dosing strategies in patients with acute COVID-19(Day 1:750 mg BID,Days 2-5:500 mg BID,CQ phosphate),patients with moderate COVID-19(Day 1:750 mg and 500 mg,Days 2-3:500 mg BID,Days 4-5:250 mg BID,CQ phosphate),and other vulnerable populations(e.g.,renal and hepatic impairment and elderly patients,Days 1-5:250 mg BID,CQ phosphate).A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

关键词： COVID-19 Chloroquine phosphate PBPK Dosing strategy

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Advances in Ophthalmology Practice and Research 2024年第2期4卷 98-105页

作者： Xiaojun Ju Alexander C.Rokohl xueting Li Yongwei Guo Ke yao Wanlin Fan Ludwig M.Heindl Department of Ophthalmology University of CologneFaculty of Medicine and University Hospital CologneCologneGermany Center for Integrated Oncology(CIO) Aachen-Bonn-Cologne-DuesseldorfCologneGermany Eye Center The Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang Provincial Key Laboratory of OphthalmologyZhejiang Provincial Clinical Research Center for Eye DiseasesZhejiang Provincial Engineering Institute on Eye DiseasesHangzhouZhejiangChina

Purpose:To explore the role of ultraviolet radiation(UVR)in the occurrence and development of various ocular ***:In this article,we retrieved ocular malignancy data from the Global Cancer Observatory(GCO)and performed correlation analysis with the global UV index and sunshine *** searched for associated studies using the following databases:Embase,Pubmed,Cochrane Library,and Google *** conducted the literature by searching the Mesh terms denoting an exposure of interest("UV radiation","ultraviolet rays",and"ocular malignancies"),All studies included are published until December 30,2023 without language ***:The mechanisms and epidemiological statistics of UVR on the onset and progression of eyelid malig-nancies are the most studied and *** role of UVR in conjunctival melanoma is similar to that in eyelid *** relationship between uveal melanoma and UVR is controversial,however,it may have at least a certain impact on its *** causes ocular surface squamous neoplasia by further activating HPV ***:UVR is a decisive risk factor for ocular malignancies,but the incidence of ultraviolet-induced tumors is also affected by many other factors.A correct and comprehensive understanding of the mechanisms of UVR in the pathogenesis of ocular malignant tumors can provide patients with more effective and selective immune regulation strategies.

关键词： Ultraviolet radiation Eyelid malignancies Conjunctival melanoma Uveal melanoma Ocular surface squamous neoplasia

Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19

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Science China(Life Sciences) 2021年第4期64卷 660-663页

作者： Qiuyu Li Cheng Cui Fei Xu Jianping Zhao Nan Li Haichao Li Tianbing Wang Hua Zhang Na Liu Yudong Wei Xiaoye Niu Yan Xu Jianping Dong xueting yao Xiaohong Wang Yahong Chen Haiyan Li Chunli Song Jie Qiao Dongyang Liu Ning Shen Department of Respiratory and Critical Care Medicine Peking University Third HospitalBeijing 100191China Drug Clinical Trial Center Peking University Third HospitalBeijing 100191China Deparment of Respiratory and Critical Care Medicine the First Afiliated Hospital of Nanchang UniversirNanchang 300060 China Department of Respiratory and Critical Care Medicine Tongi HospitalTongii Medical CollegeHuazhong Universiy of Science and TechnologyWuhan 430030China Research Center of Clinical Epidemiology Peking University Third HospitalBejing 100191China Department of Respiratory and Critical Care Medicine Peking University First HospitalBeijing 100034China Trauma Center Peking University People's HospitalBeijing 100044China Beijing Haidian Hospital Haidian Section of Peking University Third HospitalBeijing 100080Chima Deparment of Cardiology Peking University Third Hospital Beijing 100191China Instiute of Medical Innovation Peking University Third HospitalBejing 100191China

Dear Editor,Since December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has been rapidly spreading *** and chloroquine are candidates for the treatment of coronavirus disease 2019(COVID-19)owing to ... 详细信息

关键词： acute respiratory patients

A Physiologically Based Pharmacokinetic Model of HSK3486 and Extrapolation to Special Populations and Drug-Drug Interactions

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A Physiologically Based Pharmacokinetic Model of HSK3486 and...

MRI在检测高血压患者主动脉顺应性中的作用探讨

2018年中国药理学会定量药理学专业委员会学术年会

作者： xueting yao Pangke Yan Nan Wu Shiping Ma Ji Jiang Dongyang Liu Pei Hu Phase I Unit Clinical Pharmacology Research CenterPeking Union Medical College Hospital and Chinese Academy of Medical Sciences

Objectives:HSK3486 is a novel optically 2,6-disubstituted alkylphenol as general anesthetics,it is widely metabolized by CYP450 enzymes in human *** purpose of this study is to develop a physiologically based pharmacokinetic(PBPK) model for HSK3486 to provide insights into its pharmacokinetic properties in special population(liver cirrhosis,renal failure patient and geriatric),and to explore the potential risks of drug-drug interaction(DDI).Methods:Based on the platform of Simcyp population-based simulator(versin 16 and 17,Sheffield,UK),drug physicochemical properties such as molecular weight(M.W),oil-water partition coefficients(log P),free fraction in human plasma(f),and drug elimination data like in vitro intrinsic clearance(CL) by recombinant CYP1 A2,CYP2 A6,CYP2 B6,CYP2 C8,CYP2 C9,CYP2 C19,CYP2 D6,CYP2 E1,CYP3 A4,CYP3 A5 enzymes,as well as drug distribution data were integrated to develop a PBPK *** initial model was validated using observed pharmacokinetic data in Chinese healthy ***,the validated model was used to extrapolate the pharmacokinetic profiles in special population by replacing population module in Simcyp ***,inhibitors or inducers for the key metabolic enzymes of HSK3486 were selected and integrated into PBPK *** pharmacokinetic profiles were separately simulated for a single dose of HSK3486 alone and combination after 7 days successive administration of *** area under the curve(AUC) ratio with or without inhibitor was calculated for evaluate the DDI ***:The validation results demonstrated that the PBPK model could accurately predict the pharmacokinetic characteristics of HSK3486 in Chinese *** simulated pharmacokinetic parameters such as maximum concentration(C) and AUC of HSK3486 were within 1.5-fold of that *** AUC ratio of HSK3486 at presence and absence inhibitors or inducers were ranged from 0.94 to ***:A PBPK model was successfully developed to

关键词： PBPK Drug-drug interaction HSK3486 Pharmacokinetics

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河北医学 2014年第12期20卷 2035-2038页

作者：姚雪婷湖北省武汉市第三医院中医科湖北武汉430060

目的:探讨分析高血压患者主动脉顺应性中的MRI检测的临床作用。方法:计算机检索随机选取30例2013年3月至2014年3月期间在我院的高血压病患者作为本次研究的高血压组,另计算机检索随机选取30例同时期与我院体检的正常人为对照组。给予两... 详细信息

目的:探讨分析高血压患者主动脉顺应性中的MRI检测的临床作用。方法:计算机检索随机选取30例2013年3月至2014年3月期间在我院的高血压病患者作为本次研究的高血压组,另计算机检索随机选取30例同时期与我院体检的正常人为对照组。给予两组患者MRI检测,测量两组患者的收缩压和舒张压,比较两组患者的检测有效率,并计算主动脉顺应性的相关参数。结果:高血压组患者的总有效率(100.00%)高于对照组患者(70.00%),高血压组患者的血压高于对照组患者(P<0.05),两组患者的数据差异均具有统计学意义。结论:在高血压患者的主动脉顺应性的相关检测中,MRI具有较高的临床价值,准确可靠,值得临床的进一步推广与应用。

关键词： MRI 高血压主动脉顺应性

2012—2017年广西壮族自治区市售食品中沙门菌监测数据分析

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中国食品卫生杂志 2019年第5期31卷 449-455页

作者：姚雪婷蒋玉艳谭冬梅吕素玲广西壮族自治区疾病预防控制中心

目的了解广西市售食品中沙门菌污染状况和特征,为减少污染和防控食源性疾病提供科学依据。方法 2012-2017年从广西14个市采集14类市售食品共60 174份,其中生鲜类食品5 712份,即食食品54 462份,按照GB 4789. 4-2010《食品安全国家标准... 详细信息

目的了解广西市售食品中沙门菌污染状况和特征,为减少污染和防控食源性疾病提供科学依据。方法 2012-2017年从广西14个市采集14类市售食品共60 174份,其中生鲜类食品5 712份,即食食品54 462份,按照GB 4789. 4-2010《食品安全国家标准食品微生物学检验沙门氏菌检验》方法进行沙门菌检验。结果生鲜类食品中生肉及生肉制品、生水产品及其制品、速冻米面制品、鲜蛋类沙门菌检出率分别为10. 3%(399/3 883)、6. 2%(50/806)、0. 5%(2/440)、0. 0%(0/583),即食食品中熟肉制品、餐饮食品、生食蔬菜及其制品沙门菌检出率分别为0. 6%(58/10 175)、0. 3%(39/14 721)、1. 0%(5/489),焙烤及油炸类食品、饮料、水果及其制品均为0. 1%,熟蛋制品、豆制品、冷冻饮品、调味品均未检出。生肉及生肉制品共检出51种血清型,德尔卑沙门菌为优势血清型(16. 2%,70/432),主要在生猪肉中检出。即食食品共检出32种血清型,德尔卑沙门菌为优势血清型(14. 5%,11/76),主要在熟肉制品中检出。结论生鲜类受沙门菌污染最严重的食品是生畜肉和生禽肉,即食食品受沙门菌污染较严重食品是凉拌类食品。应加强从农场到餐桌的食品安全防控,减少食源性疾病的发生。

关键词：沙门菌食品检出率风险监测食源性致病菌

2011-2016年广西壮族自治区市售婴幼儿食品食源性致病菌监测结果分析

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中国食品卫生杂志 2020年第3期32卷 288-293页

作者：姚雪婷赵鹏蒋玉艳李秀桂韦程媛广西壮族自治区疾病预防控制中心广西南宁530028

目的了解广西壮族自治区婴幼儿食品中食源性致病菌污染状况和趋势,为有效开展食源性疾病防控提供科学依据。方法2011-2016年从广西壮族自治区14个市采集婴幼儿食品,按照GB 4789系列标准和《2014年国家食品污染和有害因素风险监测工作手... 详细信息

目的了解广西壮族自治区婴幼儿食品中食源性致病菌污染状况和趋势,为有效开展食源性疾病防控提供科学依据。方法2011-2016年从广西壮族自治区14个市采集婴幼儿食品,按照GB 4789系列标准和《2014年国家食品污染和有害因素风险监测工作手册》规定方法分别进行4种致病菌检验。结果共检测7956份样品,其中婴幼儿谷类辅助食品阳性率为6.1%(249/4084),婴幼儿配方食品阳性率为4.7%(183/3872)。不同年度监测结果显示,婴幼儿谷类辅助食品中,阪崎肠杆菌阳性率范围为2.7%~5.6%,蜡样芽胞杆菌为2.3%~8.4%(除2011和2015年),金黄色葡萄球菌为0.0%~0.4%;婴幼儿配方食品中,阪崎肠杆菌阳性率范围为0.2%~1.8%,蜡样芽胞杆菌为10.2%~12.4%(除2011和2015年),金黄色葡萄球菌为0.0%~0.3%;沙门菌检出1份,产地为内蒙古自治区。婴幼儿谷类辅助食品中,国内阳性率为6.1%(248/4077),7份国外样品检出1份阳性样品;婴幼儿配方食品中,国内阳性率为4.7%(177/3758),国外为5.3%(6/114)。结论广西壮族自治区市售婴幼儿食品中阪崎肠杆菌和蜡样芽胞杆菌污染持续存在,对婴幼儿食品安全造成威胁,应加强对国内生产企业的卫生监管。

关键词：食源性致病菌婴幼儿食品监测

古新世-始新世极热事件南阳盆地湖相沉积物的岩石磁学研究

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第四纪研究 2024年第5期44卷 1215-1224页

作者：梁耀王学婷陈祚伶中国科学院地质与地球物理研究所中国科学院新生代地质与环境重点实验室北京100029 中国科学院大学北京100049

古新世-始新世极热事件(PETM)是发生在早新生代的一次历时短暂的快速增温事件,该事件的主要地质特征为大幅度碳同位素负漂(CIE),表明当时有巨量富12C的轻碳注入海气系统,其排放场景与当今人类碳排放非常相似,故对这类事件的研究有重要... 详细信息

古新世-始新世极热事件(PETM)是发生在早新生代的一次历时短暂的快速增温事件,该事件的主要地质特征为大幅度碳同位素负漂(CIE),表明当时有巨量富12C的轻碳注入海气系统,其排放场景与当今人类碳排放非常相似,故对这类事件的研究有重要的现实意义。已有研究表明,磁性矿物的产生、保存与气候环境变化之间有密切关系,因此,通过对PETM时期沉积岩磁学参数的研究,可以揭示增温背景下古环境演化的时空特征。前人利用磁学方法研究海相沉积物时发现,PETM时期磁学信号出现显著响应,但不同研究区域的具体驱动机制有所差异。本研究对南阳盆地湖相PETM地层开展磁学分析,测量岩石磁学参数,发现PETM时期沉积岩磁性有所增强,磁铁矿含量增加,直到极热事件结束后才缓慢恢复到背景水平,说明事件发生前、发生期间和事件结束后的湖泊环境经历了氧化→弱还原→氧化这3个阶段,且陆相与海相沉积物对PETM具有相似的磁学响应机制。

关键词：古新世-始新世极热事件(PETM) 南阳盆地一阶反转曲线主成分分析等温剩磁分解氧化还原

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广西学生餐食源性致病菌污染状况调查

中国学校卫生 2016年第11期37卷 1688-1689,1693页

作者：姚雪婷刘展华李秀桂广西壮族自治区疾病预防控制中心食品安全风险监测与评价所南宁530028

目的了解广西学校学生餐食源性致病菌污染状况,为食源性疾病的预防和控制提供依据。方法 2014年从广西7个市和19个县的幼儿园和大中小学采集统一供应的早餐和午餐样品520份,按照国家标准进行蜡样芽胞杆菌、金黄色葡萄菌、单核细胞增生... 详细信息

目的了解广西学校学生餐食源性致病菌污染状况,为食源性疾病的预防和控制提供依据。方法 2014年从广西7个市和19个县的幼儿园和大中小学采集统一供应的早餐和午餐样品520份,按照国家标准进行蜡样芽胞杆菌、金黄色葡萄菌、单核细胞增生李斯特菌、致泻大肠埃希菌、沙门菌检验。结果学生餐样品中蜡样芽胞杆菌检出率为15.54%,金黄色葡萄球菌检出率为1.92%,单核细胞增生李斯特菌检出率为0.19%,致泻大肠埃希菌检出率为0.76%,未检出沙门菌;市级和县级学生餐食品的致病菌检出率分别为13.51%和14.29%;早餐和午餐的检出率分别为10.12%和15.63%;第一季度无致病菌,第二、三季度的致病菌检出率(15.55%和18.55%)均高于第四季度(8.63%)。结论广西学生餐存在不同程度食源性致病菌污染,应在重点季度加强学生餐食品安全监管,防止学校食物中毒事件的发生。

关键词：食品食品污染公共卫生管理