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

• 批准号: 8730022
• 负责人: JOEL REID
• 金额: $ 5.91万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 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/8730022
• 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; cancer therapy; cell preparation; design; human disease; in vivo; intraperitoneal; metabolic abnormality assessment; nonhuman primate; pharmacokinetic model; pre-clinical; preclinical efficacy; subcutaneous; tumor; urinary

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NCI癌症治疗部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。大多数选择的化合物是潜在的抗癌药物，但有些是广泛的流行和罕见的人类疾病的假定治疗药物。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)开发用于定量血浆、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)不同给药途径和时间给药后的药代动力学特性；(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。从这些药代动力学调查中获得的特征将用于进一步开发的药物的优先级和选择；在临床前疗效和毒理学研究的设计；在监管机构提交的文件中支持选定药物的临床试验。