Using Clinical Pharmacology Principals in the Developmen

在开发中使用临床药理学原理

• 批准号: 6756270
• 负责人: William Douglas Figg
• 金额: --
• 依托单位: DIVISION OF CLINICAL 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/6756270
• 关键词: angiogenesis inhibitors; antineoplastics; butyrates; camptothecin; cis platinum compound; clinical trial phase I; combination chemotherapy; cyclosporines; drug interactions; drug metabolism; drug screening /evaluation; human subject; human therapy evaluation; immunoconjugates; model design /development; neoplasm /cancer chemotherapy; paclitaxel; patient oriented research; pharmacokinetics; phenylacetates; phenylcarboxylate; suramin; thalidomide; tissue inhibitor of metalloproteinases; vinblastine; zidovudine

A successful drug development program requires a complete understanding of the clinical pharmacology of the agents being evaluated. The Clinical Pharmacology Research Core (CPRC) has as its primary interest the use of pharmacokinetic and pharmacodynamic concepts in the development of novel anticancer agents. The CPRC is directly responsible for the pharmacokinetic/pharmacodynamic analysis of numerous Phase I and II clinical trials conducted within the NCI. In addition, the CPRC provides direct pharmacokinetic support for many studies performed elsewhere in the extramural community. Within the section, we utilize compartmental and noncompartmental approaches to define the disposition of agents. Also, we are often required to characterize the plasma protein binding properties and metabolism of new agents through in vitro techniques. Several of our clinical trials have used adaptive control with a feedback mechanism to target particular plasma concentrations (e.g., suramin, CAI). The drugs with which the CPRC has had its greatest experience include: suramin, phenylacetate, phenylbutyrate, TNP-470, PMEA, AZT, PSC 833, CAI, DAB486IL2, IgG-RFB4-SMPT-dgA CD22, IgG-HD37-SMPT-dgA CD19, ormaplatin, UCN-01, flavopiridol, thalidomide, 9AC, intraperitoneal cisplatin, intraperitoneal carboplatin, docetaxel, and paclitaxel. Currently, we are characterizing the interaction between ketoconazole and docetaxel and understand the pharmacokinetics of MS275, perifosine and depsipeptide. We are currently condicting Phase I trials of CC5013 and 2ME, both angiogenesis inhibitors.

一个成功的药物开发项目需要对正在评估的药物的临床药理学有全面的了解。临床药理学研究核心（CPRC）的主要兴趣是在开发新型抗癌药物中使用药代动力学和药效学概念。CPRC直接负责在NCI内进行的多项I期和II期临床试验的药代动力学/药效学分析。此外，CPRC为在校外社区其他地方进行的许多研究提供直接的药代动力学支持。在本节中，我们利用房室和非房室方法来定义代理的处置。此外，我们经常需要通过体外技术表征新药物的血浆蛋白结合特性和代谢。我们的一些临床试验已经使用具有反馈机制的自适应控制来靶向特定的血浆浓度（例如，Suramin，CAI）。CPRC经验最丰富的药物包括：苏拉明、苯乙酸盐、苯丁酸盐、TNP-470、PMEA、AZT、PSC 833、CAI、DAB 486 IL 2、IgG-RFB 4-SMPT-dgA CD 22、IgG-HD 37-SMPT-dgA CD 19、奥马铂、UCN-01、flavopiridol、沙利度胺、9AC、腹膜内顺铂、腹膜内卡铂、多西他赛和紫杉醇。目前，我们正在表征酮康唑和多西他赛之间的相互作用，并了解MS 275、哌立福新和缩酚酸肽的药代动力学。我们目前正在进行CC 5013和2 ME的I期试验，这两种药物都是血管生成抑制剂。