Preclinical Pharmacokinetic and Pharmacological Studies of Antitumor and other Th

这份合同提供了一个资源，用于进行临床前药理学、药代动力学和新陈代谢研究，选择由NCI癌症治疗部门开发的候选治疗药物。所选择的大多数化合物都是潜在的抗癌药物，但也有一些可能是治疗广泛的流行和孤儿人类疾病的药物。根据本合同选择进行研究的化合物来自学术研究人员、制药公司或其他人提交给NCI的同行评审申请。根据合同开展的工作可能包括：(1)开发量化血浆、尿液和其他生物基质中化合物的分析方法；(2)血浆稳定性和蛋白质结合研究；(3)通过各种途径和时间表给药后的药代动力学特征；(4)对体内和各种体外系统产生的药物代谢物进行量化和鉴定；(5)评估在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被用于进一步开发的药物的优先次序和选择；临床前疗效和毒理学研究的设计；以及支持选定药物的临床试验的监管提交。

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.