Core C

核心C

基本信息

批准号：
8102899
负责人：
Jeffrey Scott Barrett
金额：
$ 25.44万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-01 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8102899
关键词：
AIDS neuropathy Acquired Immunodeficiency Syndrome Address Adult Animal Experiments Animals Atazanavir Back Basic Science Biological Biological Assay Biological Markers Biometry Biostatistics Core Cell Line Cell physiology Cells Characteristics Chemical Structure Chemicals Clinical Clinical Pharmacology Clinical Trials Clinical Trials Design Collection Computer Simulation Data Data Analyses Data Collection Databases Depressed mood Detection Development Disease Disease Progression Documentation Dose Drug Combinations Drug Interactions Drug Kinetics Ensure Environment Generations Genetic HIV High Pressure Liquid Chromatography Human In Vitro Information Systems Label Laboratories Lead Left Libraries Literature Lopinavir/Ritonavir Manuscripts Maps Mass Spectrum Analysis Measurement Mental Depression Metabolic Metadata Methodology Methods Metric Modeling Modification Molecular Weight Nature Organism Outcome Patient Selection Patients Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Pharmacotherapy Plasma Population Process Property Protocols documentation Psychometrics Reaction Time Recommendation Report (document)Research Research Design Research Personnel Resolution Resources Ritonavir Role Safety Sample Size Sampling Scheme Screening procedure Secure Signal Transduction Site Source Staging Stimulus Substance P Substance P Receptor System Therapeutic Time Tissues Toxic effect Urine Validation Variant Vertebral column Viral Viral Load result abstracting analytical method aprepitant base candidate selection chemical fingerprinting computerized data processing data integration data management data sharing design drug candidate drug discovery healthy volunteer indexing instrument interest member metabolomics microbial alkaline proteinase inhibitor models and simulation novel patient population pharmacodynamic model population based pre-clinical programs radiochemical research study response simulation small molecule symposium virology

AIDS neuropathy Acquired Immunodeficiency Syndrome Address Adult Animal Experiments Animals Atazanavir Back Basic Science Biological Biological Assay Biological Markers Biometry Biostatistics Core Cell Line Cell physiology Cells Characteristics Chemical Structure Chemicals Clinical Clinical Pharmacology Clinical Trials Clinical Trials Design Collection Computer Simulation Data Data Analyses Data Collection Databases Depressed mood Detection Development Disease Disease Progression Documentation Dose Drug Combinations Drug Interactions Drug Kinetics Ensure Environment Generations Genetic HIV High Pressure Liquid Chromatography Human In Vitro Information Systems Label Laboratories Lead Left Libraries Literature Lopinavir/Ritonavir Manuscripts Maps Mass Spectrum Analysis Measurement Mental Depression Metabolic Metadata Methodology Methods Metric Modeling Modification Molecular Weight Nature Organism Outcome Patient Selection Patients Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Pharmacotherapy Plasma Population Process Property Protocols documentation Psychometrics Reaction Time Recommendation Report (document)Research Research Design Research Personnel Resolution Resources Ritonavir Role Safety Sample Size Sampling Scheme Screening procedure Secure Signal Transduction Site Source Staging Stimulus Substance P Substance P Receptor System Therapeutic Time Tissues Toxic effect Urine Validation Variant Vertebral column Viral Viral Load result abstracting analytical method aprepitant base candidate selection chemical fingerprinting computerized data processing data integration data management data sharing design drug candidate drug discovery healthy volunteer indexing instrument interest member metabolomics microbial alkaline proteinase inhibitor models and simulation novel patient population pharmacodynamic model population based pre-clinical programs radiochemical research study response simulation small molecule symposium virology

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项目摘要

Core C, Quantitative Pharmacology and Biostatistics, will provide pharmacology and biostatistics support to all projects in the application. The Core is composed of three complementary components (quantitative analysis, modeling/simulation and biostatistics/data management) that serve the five Core aims. Aim 1: To develop bioanalytical methods to detect drug and biomarker exposure. Develop analytical methods to detect NKIR antagonist drug candidates in various biologic matrices in human and animal experiments. Develop biomarker assays (substance P and other neurokinins) to support both preclinical and clinical projects. Aim 2: To identify potential novel biomarkers of drug activity, subject characteristics correlated to therapeutic response and time-dependent markers of disease progression via metabolomic and metabonomic support. Determine metabolic differences in healthy volunteers, depressed and HIV-infected patients (with and without depression); assess metabolic time course in Neuro AIDS patients. Aim 3: To provide in silico ADME screens and decision criteria for drug candidates. Assess and rank "druggability" metrics generated from in vitro attributes and physiochemical data from HTS. Assess drug interaction potential for candidate combinations to be studied In animal and human trials. Aim 4: To provide pharmacokinetic (PK) and pharmacodynamic (PD) support for dose targeting in animal and human trials; develop PK, PD and disease progression models to define the therapeutic window for clinical candidates. PK/PD modeling to support dose selection for patient trials. Population-based PK/PD modeling to understand sources of variation in drug kinetics and viral dynamics. Disease progression modeling incorporating metabonomic indices along with clinical response and disease status. Clinical trial simulation to facilitate optimal sampling and trial design. Aim 5: To provide information systems, data management and biostatistics support to all projects and cores. Assist in the design and interpretation of preclinical/clinical experiments; support sample size requirements. Design and maintain a database to accommodate projects and cores. Manage, verify and maintain data; implement data sharing plan.

核心C，定量药理学和生物统计学将为药理学和生物统计学提供支持应用程序中的所有项目。核心由三个互补成分组成（定量为五个核心目的服务的分析，建模/仿真和生物统计学/数据管理）。目的1：开发生物分析方法来检测药物和生物标志物暴露。发展分析检测人和动物中各种生物学基质中NKIR拮抗剂候选物的方法实验。开发生物标志物测定（物质P和其他神经蛋白），以支持临床前和临床项目。目的2：确定潜在的新型药物活性生物标志物，主题特征与治疗相关疾病进展的反应和时间依赖性标记通过代谢组和替代支持。确定健康志愿者，抑郁症和HIV感染患者的代谢差异（与没有抑郁）；评估神经艾滋病患者的代谢时间课程。 AIM 3：在Silico Adme屏幕上提供候选药物的决策标准。评估和排名来自HTS的体外属性和理化数据产生的“可药物性”指标。评估药物在动物和人类试验中研究候选组合的相互作用潜力。目标4：提供药代动力学（PK）和药效（PD）支持动物剂量的靶向剂量和人类试验；开发PK，PD和疾病进展模型来定义治疗窗口临床候选人。 PK/PD建模以支持患者试验的剂量选择。基于人群的PK/PD 建模以了解药物动力学和病毒动力学变化的来源。疾病进展纳入纳入替代指数以及临床反应和疾病状态的建模。临床试验模拟以促进最佳采样和试验设计。目标5：为所有项目和核心提供信息系统，数据管理和生物统计学支持。协助临床前/临床实验的设计和解释；支持样本量的要求。设计和维护数据库以容纳项目和核心。管理，验证和维护数据；实施数据共享计划。