检索结果-南通市图书馆

Simulation-based simplification of target-mediated drug disposition model of denosumab

在线全文

cnki会议

学校读者我要写书评

暂无评论

Journal of Chinese Pharmaceutical Sciences 2018年第11期27卷 767-776页

作者： Yu Fu Ye Yao Peiming Ma Xuan Zhou Wei Lu Tianyan Zhou Beijing Key Laboratory of Molecular Pharmaceutics and New drug Delivery System Department of PharmaceuticsSchool of Pharmaceutical SciencesPeking University Health ScienceCenterBeijing 100191China GSK Research and Development Shanghai 201203China

Target-mediated drug disposition (TMDD)model is one of the main modeling theories for studying nonlinear pharmacokinetics (PK)ofmonoclonal ***,there are too many parameters in full TMDD model to be estimated based on limited clinical data,leading to instability of the final *** the present study,we analyzed the predictive ability and applicability of a simplified quasi-steady state (QSS)model with the assumption that the total target concentration was a constant parameter during treatment with monoelonal antibody in clinical data *** on the parameters of a published TMDD model of denosumab,simulations were performed at population and individual ***,a simplified TMDD model,QSS model, was used to examine the effects of hypotheses,in which the total receptor concentration was constant or variable on model fit and stability of parameter *** simulations at the population level and model fit results of simulated individual data showed that at the therapeutic doses,the total receptor concentration had little influence on changes in drug concentration,and the model with constant total receptor concentration had the same predictive *** validated hypothesis could be applied to clinical trial design and selection of the optimal PK model in the development of monoclonal antibodies.

关键词： Target-mediated drug disposition model Monoclonal antibody Nonlinear pharmacokinetics Denosumab Simulation

Quantitation of DNA by nuclease P1 digestion and UPLC-MS/MS to assess binding efficiency of pyrrolobenzodiazepine

在线全文

学校读者我要写书评

暂无评论

Journal of Pharmaceutical Analysis 2020年第3期10卷 247-252页

作者： Yong Ma Buyun Chen Donglu Zhang drug Metabolism and disposition Genentech1 DNA WaySouth San FranciscoCA94080USA

Accurate DNA quantitation is a prerequisite in many biomedical and pharmaceutical *** we established a new DNA quantitation method by nuclease P1 digestion and UPLC-MS/MS *** fragments can be efficiently hydrolyzed to single deoxyribonucleotides by nuclease P1 in a short *** decent stabilities of all the four deoxyribonucleotides were confirmed under different *** monophosphate(dAMP)was selected as the surrogate for DNA quantitation because dAMP showed the highest sensitivity among the four deoxyribonucleotides in the UPLC-MS/MS *** linear range in DNA quantitation by this method is 1.2-5000 ng/*** the validation,the inter-day and intra-day accuracies were within 90%-110%,and the inter-day and intra-day precision were acceptable(RSD<10%).The validated method was successfully applied to quantitate DNA isolated from tumors and organs of a mouse xenograft *** to the quantitation methods using UV absorbance,the reported method provides an enhanced sensitivity,and it allows for the accurate quantitation of isolated DNA with contamination of RNA and ribonucleotide.

关键词： Nuclease P1 UPLC-MS/MS DNA quantitation DNA alkylation Pyrrolobenzodiazepine(PBD-Dimer)

QUANTITATIVE PHARMACOLOGY The Next Evolution in Model Based drug Development

在线全文

学校读者我要写书评

暂无评论

QUANTITATIVE PHARMACOLOGY The Next Evolution in Model Based ...

药物非临床安全性研究学术研讨会

作者： S.R.B.Allerheiligen Ph.D.drug disposition:ADME and Global PK/PD

Questions ·How do we assure we are developing the right chemical candidate? ·What is the therapeutic index? ·What is the dose response for efficacy? Safety? How do we individualize doses for the patient?

关键词：

Metabolites in Safety Testing(MIST):A Case Study-Compound X

在线全文

cnki会议

学校读者我要写书评

暂无评论

Metabolites in Safety Testing(MIST):A Case Study-Compound X

药物非临床安全性研究学术研讨会

作者： Lisa A．Shipley drug disposition Global PK/PD and Trial Simulation Eli Lilly and Company Ph.D Vice President

Background Increased attention by industry and regulators to role of metabolites as potential mediators of toxicity Variable interactions with regulators on when and how to evaluate metabolites

关键词：

Optimizing aerosolization of a high-dose L-arginine powder for pulmonary delivery

在线全文

cnki会议

学校读者我要写书评

暂无评论

Asian Journal of Pharmaceutical Sciences 2015年第6期10卷 528-540页

作者： Satu Lakio David A.V.Morton Anna P.Ralph Pete Lambert drug Delivery Disposition and DynamicsMonash Institute of Pharmaceutical SciencesMonash University381 Royal ParadeParkvilleVictoria 3052Australia Global and Tropical Health Division Menzies School of Health ResearchDarwinNorthern TerritoryAustralia Department of Medicine Royal Darwin HospitalDarwinNorthern TerritoryAustralia AstraZeneca R&D Pepparedsleden 143183 MölndalSweden

In this study a carrier-free dry powder inhalation(DPI)containing L-arginine(ARG)was *** such,it is proposed that ARG could be used for adjunctive treatment of cystic fibrosis and/or *** processing methods were used to manufacture highdose formulation batches consisting various amounts of ARG and *** formulations were evaluated using several analytical methods to assess suitability for further *** batches had enhanced in vitro aerolization *** future challenges include the highly hygroscopic nature of unformulated ARG powder and identifying the scale of dose of ARG required to achieve the response in lungs.

关键词： Pulmonary delivery L-arginine Spray drying Mechanofusion Dry powder inhaler(DPI) Formulation

Impact of Social Media Challenges on Pediatric Single-Use Detergent Sacs and Diphenhydramine Ingestions Reported to United States Poison Control Centers

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Open Journal of Emergency Medicine 2024年第3期12卷 104-113页

作者： Lea Dikranian Varun Vohra David Merolla Usha Sethuraman Nirupama Kannikeswaran Department of Emergency Medicine Children’s Hospital of Michigan Detroit USA Michigan Poison & drug Information Center Department of Emergency Medicine Wayne State University School of Medicine Detroit USA Department of Sociology Wayne State University School of Medicine Detroit USA Department of Emergency Medicine Central Michigan University Detroit USA

Background : Social media platforms are popular among children and often feature challenges that become viral. Notably, the Tide Pod ® and Benadryl ® challenges encouraged viewers to ingest these substances for their visual appeal and hallucinogenic effects, respectively. This study aimed to assess the clinical impact and outcomes of single-use detergent sacs (SUDS) and diphenhydramine challenges on pediatric ingestions reported to United States (U.S.) Poison Control Centers (PCCs). Methods : We conducted a retrospective review of pediatric exposures reported to U.S. PCCs using data from the National Poison Data System (NPDS). The study included intentional single-substance ingestions of both brand-name and generic forms of SUDS and diphenhydramine among children ≤ 19 years. We compared the number of calls, clinical effects, disposition, and management strategies for SUDS (pre: 01/01/17 to 12/31/17 vs. post: 01/01/18 to 12/31/18) and diphenhydramine (pre: 08/01/19 to 07/31/20 vs. post: 08/01/20 to 07/31/21) ingestions 12 months before and after the introduction of the respective social media challenges. Differences in proportions were compared using the Chi-square test. Results : During the study period, 469 ingestions of SUDS and 5,702 ingestions of diphenhydramine were reported. Post-challenge periods saw an increase in both SUDS (pre: 82 vs. post: 387; 372% increase) and diphenhydramine ingestions (pre: 2,672 vs. post: 3,030; 13% increase). While there were no significant changes in moderate or major clinical outcomes, hospitalizations increased post-challenge for both SUDS [pre: 4 (4.9%) vs. post: 33 (8.5%); p = 0.25] and diphenhydramine [pre: n = 904 (33.8%) vs. post: 1,190 (39.3%); p < 0.001]. Conclusion : Pediatric ingestions reported to U.S. PCCs and hospitalizations increased coinciding with the introduction of Tide Pod ® and Benadryl ® challenges. While causality cannot be definitively established, it is essential for pediatricians and parents to be aware

关键词： Emergency Medicine Ingestions Toxicology Social Media Challenges Pediatrics

Screening and verifying potential NTCP inhibitors from herbal medicinal ingredients using the LLC-PK1 cell model stably expressing human NTCP

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Chinese Journal of Natural Medicines 2016年第7期14卷 549-560页

作者： SHEN Zhuo-Wei LUO Meng-Yue HU Hai-Hong ZHOU Hui JIANG Hui-Di YU Lu-Shan ZENG Su Institute of drug Metabolism and Pharmaceutical Analysis Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical Sciences Zhejiang University

NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis. In addition, recent studies have found that NTCP is a functional receptor of HBV and HDV. Therefore, it is important to study the interaction between drugs and NTCP and identify the inhibitors/substrates of NTCP. In the present study, a LLC-PK1 cell model stably expressing human NTCP was established, which was simple and suitable for high throughput screening, and utilized to screen and verify the potential inhibitors of NTCP from 102 herbal medicinal ingredients. The results showed that ginkgolic acid(GA)(13 : 0), GA(15 : 1), GA(17 : 1), erythrosine B, silibinin, and emodin have inhibitory effects on NTCP uptake of TCNa in a concentration-dependent manner. Among them, GA(13 : 0) and GA(15 : 1) exhibited the stronger inhibitory effects, with IC_(50) values being less than 8.3 and 13.5 mmol·L^(-1), respectively, than the classical inhibitor, cyclosporin A(CsA)(IC_(50) = 20.33 mmol·L^(-1)). Further research demonstrated that GA(13 : 0), GA(15 : 1), GA(17 : 1), silibinin, and emodin were not substrates of NTCP. These findings might contribute to a better understanding of the disposition of the herbal ingredients in vivo, especially in biliary excretion.

关键词： Herbal medicinal ingredients Human NTCP Inhibitor Transport Biliary excretion

Recent progress in the molecular imaging of therapeutic monoclonal antibodies

在线全文

学校读者我要写书评

暂无评论

Journal of Pharmaceutical Analysis 2020年第5期10卷 397-413页

作者： Kaifeng He Su Zeng Linghui Qian Institute of drug Metabolism and Pharmaceutical Analysis Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China

Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in *** is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are *** techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA,and tissue distribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information,while methods for characterization of antibody’s interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under *** progress in detecting therapeutic antibodies,in particular,the development of methods suitable for illustrating the molecular dynamics,is described here.

关键词： Therapeutic monoclonal antibodies Molecular structure Biological function Molecular imaging

The Role of ADME in drug Safety Evaluation

在线全文

学校读者我要写书评

暂无评论

The Role of ADME in Drug Safety Evaluation

药物非临床安全性研究学术研讨会

作者： Michelle M He Lisa A.Shipley Carl L.McMillian Ph.D.Research Advisor Drug Disposition Lilly Research LaboratorieDivision of Eli Lilly and Comp Ph.D.Vice President Drug Disposition Lilly Research LaboratorieDivision of Eli Lilly and Comp Ph.D.Director Pathology and Investigative Toxicology Lilly Research LaboratorieDivision of Eli Lilly and Comp

Role of ADME in Safety Assessment ·Delineates the Absorption,Distribution, Metabolism and Excretion of drug candidates in animals and humans ·Determines exposure in Toxicology Studies to establish Margins of Safety

关键词：