Preclinical Pharmacological Studies of Antitumor and Other Therapeutic Agents

抗肿瘤和其他治疗药物的临床前药理学研究

• 批准号: 7789054
• 负责人: MATTHEW AMES
• 金额: $ 20.23万
• 依托单位: MAYO CLINIC ROCHESTER
• 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/7789054
• 关键词: Preclinical; Pharmacological; Studies; Antitumor; Other

This contract (Mayo Clinics) provides a resource for conducting preclinical pharmacology, pharmacokinetic, and metabolism studies with candidate therapeutic agents selected for development by the Developmental Therapeutics Program, NCI. Most of the compounds selected are potential anticancer agents (including those relevant to orphan cancers), but some are putative therapeutics for a wide range of prevalent and orphan human diseases. Compounds selected for study under this contract may arise from a variety of peer-reviewed extramural sources such as the Division of Cancer 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 is a source of anticancer compounds for study. Work carried out under the contract may include: (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 these 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.

该合同（马约诊所）提供了一种资源，用于对NCI开发治疗项目选定的候选治疗药物进行临床前药理学、药代动力学和代谢研究。所选的大多数化合物是潜在的抗癌剂（包括与孤儿癌症相关的那些），但有些化合物是广泛的流行和孤儿人类疾病的推定治疗剂。根据本合同选择用于研究的化合物可能来自各种同行评审的校外来源，例如癌症治疗药物开发组（DDG）的潜在NCI持有的研究性新药（IND）申请和快速访问干预开发（RAID）和快速访问NCI发现资源（R*A*N*D）计划。此外，开发项目也来自其他渠道，如NCI临床成像剂和增强剂开发（DCIDE）计划，NIDDK 1型糖尿病RAID计划和NIH路线图RAID计划（为许多治疗类别的候选药物开发提供支持）。NCI的校内项目是抗癌化合物的研究来源。 根据合同开展的工作可包括：（1）开发分析方法，以量化血浆、尿液和其他生物基质中的化合物，使其达到预期的治疗和/或毒性范围;（2）血浆稳定性和蛋白质结合研究，在化合物开发的早期阶段进行，以确保适当的样品处理，并帮助解释动物研究;（3）通过各种途径和时间表给予动物后的药代动力学表征，包括在适当时测定口服生物利用度;（4）体内和各种体外系统（例如，S9组分、微粒体、肝细胞、P450亚型、肝切片）;和（5）评估肿瘤或替代组织中的药效学效应，以及这些效应与药物水平和/或总药物暴露的相关性。 预计从这些药代动力学研究中获得的数据将有助于设计选定药物的临床前疗效和毒理学研究以及I期临床试验。承包商提交的技术报告将包含在NCI或其他机构提交给FDA的IND中。