Clinical Pharmacology

临床药理学

• 批准号: 7064476
• 负责人: William Douglas Figg
• 金额: --
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7064476
• 关键词: analytical method; antineoplastics; clinical research; dosage; drug administration routes; drug interactions; drug metabolism; drug screening /evaluation; enzyme activity; human subject; method development; model; pharmacokinetics; pharmacology; protein binding; tissue /cell culture; toxicology

To characterize the clinical pharmacology of a given agent we take the following step-wise approach: development of an analytical method for quantitation in biological fluids; characterization of pharmacokinetics; pharmacokinetic modeling to govern future dosing schedules; evaluation of plasma protein binding; determination of renal elimination; in vitro metabolism studies to characterize the enzymes involved, metabolites formed and possible drug-drug interactions; development of pharmacodynamic correlations with efficacy and/or toxicity; pharmacogenetic approaches to further understand factors responsible for interindividual differences. Our research efforts have focused primarily on agents that target the aberrant biology of neoplasms (agents that target signal transduction pathways, angiogenesis inhibitors, cell cycle inhibitors, protein kinase inhibitors, antagonists of peptide growth factors) and on novel ways of administering cytotoxic agents.

为了表征给定药物的临床药理学，我们采用以下逐步方法：开发用于定量生物流体的分析方法；药代动力学的表征；药代动力学建模以控制未来的给药时间表；评估血浆蛋白结合；确定消除肾脏；体外代谢研究以表征所涉及的酶，形成的代谢以及可能的药物相互作用；与功效和/或毒性的药效学相关性的发展；进一步理解负责个体差异的因素的药物遗传学方法。我们的研究工作主要集中在靶向肿瘤异常生物学的药物上（靶向信号转导途径，血管生成抑制剂，细胞周期抑制剂，蛋白激酶抑制剂，肽生长因子的拮抗剂）和新型施用细胞毒素的方法。