Preclinical Pharmacological Studies of Antitumor & Other Therapeutic Agents

抗肿瘤的临床前药理研究

基本信息

批准号：
8328342
负责人：
PATRICIA E NOKER
金额：
$ 6万
依托单位：
SOUTHERN RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-12-15 至 2011-12-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8328342
关键词：
Animals Antineoplastic Agents 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 Malignant Neoplasms Measurement Membrane Methodology Microsomes Molecular Mus National Institute of Diabetes and Digestive and Kidney Diseases Oral Orphan Pathway interactions Peer Review Permeability Pharmaceutical Preparations Pharmacodynamics Pharmacology Phase I Clinical Trials Plasma Plasma Proteins Process Protein Binding Protein Isoforms Proteomics Rapid Access to Intervention Development Rattus Research Institute 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 Work analytical method animal tissue cancer therapy cell preparation design drug development human disease in vivo intraperitoneal metabolic abnormality assessment nonhuman primate pharmacokinetic model pre-clinical preclinical efficacy programs subcutaneous technical report tumor urinary

项目摘要

This contract (Southern Research Institute) 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（南方研究所）提供了利用国家癌症研究所发展治疗计划选择开发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的资源。大多数选定的化合物都是潜在的抗癌药物（包括与孤儿癌症相关的化合物），但有些化合物被认为是治疗多种流行和孤儿人类疾病的药物。根据本合同选择用于研究的化合物可能来自各种经过同行评审的外部来源，例如癌症治疗药物开发小组 (DDG) 部门用于 NCI 持有的潜在研究性新药 (IND) 申请和快速干预开发(RAID) 和针对研究者持有的 IND 的 NCI 发现资源快速访问 (R*A*N*D) 计划。此外，其他开发项目也来自其他渠道，例如 NCI 临床影像剂和增强剂开发 (DCIDE) 计划、NIDDK 1 型糖尿病 RAID 计划和 NIH 路线图 RAID 计划（为候选药物的开发提供支持）在许多治疗类别中）。 NCI 校内计划是用于研究的抗癌化合物的来源。根据合同开展的工作可能包括： (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，使其达到预期治疗和/或毒性范围的水平； (2) 血浆稳定性和蛋白质结合研究，这些研究在化合物开发的早期阶段进行，以确保正确的样品处理并帮助解释动物研究； (3) 通过不同途径和时间表对动物给药后的药代动力学特征，包括适当时测定口服生物利用度； (4) 体内和各种体外系统中产生的药物代谢物的定量和鉴定（例如，S9级分、微粒体、肝细胞、P450亚型、肝切片）； (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所选药物的临床前功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 或其他机构向 FDA 提交的 IND 中。