Preclinical Pharmacokinetic and Pharmacological Studies of Antitumor and other Th

这份合同提供了一个资源，用于进行非临床药理学、药代动力学和新陈代谢研究，使用由NCI癌症治疗部门选择开发的候选治疗药物。根据本合同选择进行研究的候选疗法来自学术研究人员、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包括：(1)开发分析方法，以量化生物基质中测试试剂的水平；(2)血浆稳定性和蛋白质结合研究；(3)按不同途径和时间表给药后的药代动力学特征；(4)对产生的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作用，以及这些影响与试剂水平和/或总暴露的相关性。从这些药代动力学研究中获得的特征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 nonclinical pharmacology, pharmacokinetic, and metabolism studies with candidate therapeutic agents selected for development by the Division of Cancer Treatment, NCI. Candidate therapies 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 includes: (1) development of analytical methods to quantify the levels of test agents in biological matrices; (2) plasma stability and protein binding studies; (3) pharmacokinetic characterization following administration by various routes and schedules; (4) quantification and identification of metabolites generated; and (5) assessment of pharmacodynamic effects in tumor or surrogate tissues and correlation of these effects with levels of agent and/or total exposures. The characterizations obtained from these pharmacokinetic investigations are 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.