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.

该合同为进行临床前药理学，药代动力学和代谢研究提供了一种资源，并通过癌症治疗分割NCI选择用于开发的候选治疗剂。所选的大多数化合物都是潜在的抗癌剂，但有些是针对广泛和孤儿疾病的广泛的假定治疗方法。根据该合同选择进行研究的化合物是由学术研究人员，制药公司或其他人提交给NCI的同行评审的应用。根据合同进行的工作可能包括：（1）开发分析方法来量化血浆，尿液和其他生物矩阵中的化合物；（2）血浆稳定性和蛋白质结合研究；（3）通过各种途径和时间表给动物施用后的药代动力学表征；（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；（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。从这些药代动力学研究中获得的表征将用于进一步开发的药物的优先级和选择。在临床前功效和毒理学研究的设计中；在支持选定药物的临床试验的监管提交中。