Preclinical Pharmacological Studies of Antitumor & Other Therapeutic Agents

抗肿瘤的临床前药理研究

• 批准号: 8177657
• 负责人: MERRILL J EGORIN
• 金额: $ 50.97万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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 2010-12-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8177657
• 关键词: Animals; Area Under Curve; Autopsy; Biochemical; Biological; Biological Assay; Biological Availability; Biological Models; Body Fluids; Canis familiaris; Categories; Clinical; Computing Methodologies; Continuous Infusion; Contractor; Contracts; Cytochrome P450; Data; Development; Developmental Therapeutics Program; Dose; Drug Exposure; Drug Formulations; Drug Kinetics; Drug or chemical Tissue Distribution; Enhancers; Ensure; Enzymes; Extramural Activities; Genomics; Half-Life; Hepatocyte; Human; Image; In Vitro; Institution; Insulin-Dependent Diabetes Mellitus; Intramural Research Program; Intravenous; Investigation; Investigational New Drug Application; Laboratories; Liquid substance; Liver; Maintenance; Measurement; Membrane; Methodology; Microsomes; Molecular; Mus; National Institute of Diabetes and Digestive and Kidney Diseases; Oral; Pathway interactions; Peer Review; Permeability; Pharmaceutical Preparations; Pharmacodynamics; Phase I Clinical Trials; Plasma; Plasma Proteins; Process; Protein Binding; Protein Isoforms; Proteomics; Rapid Access to Intervention Development; Rattus; Research Design; Research Personnel; Resources; Route; Sampling; Schedule; Shipping; Ships; Slice; Solubility; Solvents; Source; Staging; Structure; System; Testing; Therapeutic; Therapeutic Agents; Time; Tissue Sample; Tissues; Toxicology; Tumor Tissue; United States National Institutes of Health; Urine; analytical method; animal tissue; cell preparation; design; drug development; in vivo; intraperitoneal; metabolic abnormality assessment; nonhuman primate; pharmacokinetic model; pre-clinical; preclinical efficacy; programs; subcutaneous; technical report; tumor; urinary

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.

本合同为NCI发展治疗项目选择用于临床前开发的药物进行以下类型的研究提供了资源：(1)开发分析方法，将血浆、尿液和其他生物基质中的化合物定量到与预期治疗和/或毒性范围相对应的水平；(2)血浆稳定性和蛋白质结合研究，这是在化合物开发的早期阶段进行的，以确保正确的样品处理，并有助于解释动物研究；(3)通过各种途径和时间表给药后的药代动力学特性，包括适当情况下口服生物利用度的测定；(4)体内和各种体外系统（如S9组分、微粒体、肝细胞、P450异构体、肝切片）中产生的药物代谢物的定量和鉴定；(5)评估肿瘤或替代组织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。预计从详细的药代动力学调查中获得的数据将有助于设计临床前疗效和毒理学研究以及选定药物的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。