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: 8602503
• 负责人: LALITHA IYER
• 金额: $ 2.77万
• 依托单位: SRI INTERNATIONAL
• 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/8602503
• 关键词: Animals; Award; Biological; Biological Availability; Cytochrome P450; Development; Drug Kinetics; Ensure; Hepatocyte; In Vitro; International; Liver; Microsomes; Modification; Molecular Target; Pharmaceutical Preparations; Pharmacodynamics; Plasma; Protein Binding; Protein Isoforms; Research Design; Resources; Route; Sampling; Schedule; Slice; Staging; System; Tissues; Urine; analytical method; evaluation/testing; in vivo; pre-clinical; programs

SRI international provides a continuing resource for conducting the following types of studies with agents selected for preclinical development through the programs listed above: (1) development of sensitive analytical methods to quantify compounds in plasma, urine, tissues, and other biological matrices; (2) plasma stability and protein binding studies, which are conducted at an early stage of compound development to ensure proper sample handling and to aid in the interpretation of in vivo studies; (3) pharmacokinetic evaluation of test compounds following administration to animals by various routes and schedules, including a determination of bioavailability by various routes; (4) quantification and identification of drug metabolites generated in vivo and in various in vitro systems (S9 fractions, microsomes, hepatocytes, P450 isoforms, liver slices); and (5) correlation of compound effects on putative molecular targets (pharmacodynamic effects) with compound exposures.

SRI International 提供持续的资源，用于通过上述计划选择用于临床前开发的药物进行以下类型的研究：（1）开发灵敏的分析方法来量化血浆、尿液、组织和其他生物基质中的化合物； (2) 血浆稳定性和蛋白质结合研究，这些研究在化合物开发的早期阶段进行，以确保正确的样品处理并帮助解释体内研究； (3)通过各种途径和时间表给予动物后测试化合物的药代动力学评价，包括通过各种途径测定生物利用度； (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（S9级分、微粒体、肝细胞、P450亚型、肝切片）； (5) 化合物对推定分子靶点的影响（药效作用）与化合物暴露的相关性。