Preclinical Pharmacological Studies

临床前药理学研究

• 批准号: 7789055
• 负责人: KENNETH CHAN
• 金额: $ 53.6万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-15 至 2009-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7789055
• 关键词: Preclinical; Pharmacological; Studies

This contract provides a resource for conducting the following types of studies with agents selected for preclinical development by the Developmental Therapeutics Program, NCI: (1) development of analytical methods to quantify compounds in plasma, urine, and other biological matrices at levels corresponding to the expected therapeutic and/or toxic range; (2) plasma stability and protein binding studies, which are conducted at an early stage of compound development to ensure proper sample handling and to aid in the interpretation of animal studies; (3) pharmacokinetic characterization following administration to animals by various routes and schedules, including a determination of oral bioavailability where appropriate; (4) quantification and identification of drug metabolites generated in vivo and in various in vitro systems (e.g., S9 fractions, microsomes, hepatocytes, P450 isoforms, liver slices); and (5) assessment of pharmacodynamic effects in tumor or surrogate tissues and correlation of these effects with drug levels and/or total drug exposures. It is anticipated that the data obtained from detailed pharmacokinetic investigations will be useful in the design of preclinical efficacy and toxicology studies and Phase I clinical trials of selected agents. Technical reports submitted by the contractors will be included in INDs submitted to the FDA by the NCI or other institutions. Compounds selected for study under this contract may arise from a variety of peer-reviewed extramural sources such as the Division of Canter Treatment Drug Development Group (DDG) for potential NCI-held Investigational New Drug (IND) applications and the Rapid Access to Intervention Development (RAID) and Rapid Access to NCI Discovery Resources (R*A*N*D) Programs for investigator-held INDs. In addition, development projects also arise from other pipelines such as the NCI Development of Clinical Imaging Agents and Enhancers (DCIDE) program, the NIDDK Type-1 Diabetes RAID program, and the NIH Roadmap RAID Program (which provides support for development of candidate agents in many therapeutic categories). The NCI intramural program has also been a source of anticancer compounds for study.

该合同提供了一种资源，用于通过开发治疗计划NCI选择用于临床前开发的药物进行以下类型的研究：（1）开发分析方法，以量化与预期治疗和/或毒性范围相对应的水平的血浆，尿液和其他生物矩阵中的化合物； （2）在复合发育的早期阶段进行的血浆稳定性和蛋白质结合研究，以确保正确的样品处理并帮助解释动物研究； （3）通过各种途径和时间表对动物进行给药后的药代动力学表征，包括在适当的情况下确定口服生物利用度； （4）在体内和各种体外系统中产生的药物代谢产物的定量和鉴定（例如S9级分，微粒体，肝细胞，P450同工型，肝切片）； （5）评估肿瘤或替代组织中的药效学作用，以及这些作用与药物水平和/或总药物暴露的相关性。预计从详细的药代动力学研究获得的数据将在临床前功效和毒理学研究以及选定药物的I期临床试验的设计中有用。承包商提交的技术报告将由NCI或其他机构提交给FDA的IND中。 根据本合同选择进行研究的化合物可能来自各种同行评审的外壁外来源，例如潜在的NCI控制的NCI-HELD调查新药（IND）应用（IND）应用以及快速访问干预开发（RAID）和快速访问NCI发现资源（R*A*n*d）的INDS计划。此外，开发项目还来自其他管道，例如NCI的临床成像剂和增强剂（DCIDE）计划，NIDDK Type-1糖尿病RAID RAID计划和NIH RoadMap RAID计划（为许多治疗类别中候选者的发展提供支持）。 NCI壁内计划也是抗癌化合物的来源。