Preclinical Pharmacokinetic and Pharmacological Studies of Antitumor and other Th

抗肿瘤等药物的临床前药代动力学和药理学研究

基本信息

批准号：
8497527
负责人：
LALITHA IYER
金额：
$ 21.09万
依托单位：
SRI INTERNATIONAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8497527
关键词：
Animals Antineoplastic Agents Area Under Curve Biochemical Biological Biological Assay Biological Availability Biological Models Body Fluids Canis familiaris Clinical Trials Computing Methodologies Continuous Infusion Contracts Data Development Drug Exposure Drug Formulations Drug Kinetics Drug or chemical Tissue Distribution Elements Enzymes Half-Life Human In Vitro Intravenous Investigation Laboratories Liquid substance Liver Membrane Molecular Mus Oral Orphan Pathway interactions Peer Review Permeability Pharmaceutical Preparations Pharmacodynamics Pharmacologic Substance Pharmacology Plasma Plasma Proteins Process Protein Binding Rattus Research Personnel Resources Route Sampling Schedule Solubility Solvents Structure System Testing Therapeutic Therapeutic Agents Tissues Toxicology Tumor Tissue Urine Validation Work analytical method animal tissue base cancer therapy cell preparation design human disease in vivo intraperitoneal metabolic abnormality assessment nonhuman primate pharmacokinetic model pre-clinical preclinical efficacy subcutaneous tumor urinary

项目摘要

This contract provides a resource for conducting preclinical pharmacology, pharmacokinetic, and metabolism studies with candidate therapeutic agents selected for development by the Division of Cancer Treatment, NCI. Most of the compounds selected are potential anticancer agents, but some are putative therapeutics for a wide range of prevalent and orphan human diseases. Compounds selected for study under this contract arise from peer-reviewed applications submitted to NCI by academic investigators, pharmaceutical companies, or others. Work carried out under the contract may include: (1) development of analytical methods to quantify compounds in plasma, urine, and other biological matrices; (2) plasma stability and protein binding studies; (3) pharmacokinetic characterization following administration to animals by various routes and schedules; (4) quantification and identification of drug metabolites generated in vivo and in various in vitro systems; and (5) assessment of pharmacodynamic effects in tumor or surrogate tissues and correlation of these effects with drug levels and/or total drug exposures. The characterizations obtained from these pharmacokinetic investigations will be used in the prioritization and selection of agents for further development; in the design of preclinical efficacy and toxicology studies; and in regulatory submissions in support of clinical trials of selected agents.

该合同为使用 NCI 癌症治疗部门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提供了资源。大多数选定的化合物都是潜在的抗癌药物，但也有一些被认为是治疗多种流行病和罕见人类疾病的药物。根据本合同选择用于研究的化合物来自学术研究人员、制药公司或其他机构提交给 NCI 的同行评审申请。根据合同开展的工作可能包括： (1) 开发定量血浆、尿液和其他生物基质中化合物的分析方法； (2)血浆稳定性和蛋白结合研究； (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； (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； (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。从这些药代动力学研究中获得的特征将用于确定进一步开发药物的优先顺序和选择；临床前疗效和毒理学研究的设计；以及支持选定药物临床试验的监管提交文件。