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.

成功的药物开发计划需要完全了解正在评估的药物的临床药理学。临床药理学研究核心（CPRC）是其在新型抗癌剂开发中使用药代动力学和药效学概念的主要兴趣。 CPRC直接负责对NCI内进行的许多I和II期临床试验的药代动力学/药效学分析。此外，CPRC为在壁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，我们利用隔室和非各个区域的方法来定义代理的处置。同样，我们通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，苏拉米蛋白，CAI）。 CPRC拥有最丰富经验的药物包括：灌木，苯基乙酸，苯基丁酸，TNP-470，PMEA，AZT，PSC 833，CAI，CAI，DAB486IL2，IgG-RFB4-SMPT-SMPT-DGA CD22黄叶肽，沙利度胺，9AC，腹膜内顺铂，腹膜内carboplatin，多西他赛和紫杉醇。目前，我们正在表征酮康唑与多西他赛之间的相互作用，并了解MS275，Perifosine和Depsipeptide的药代动力学。我们目前正在宽恕CC5013和2ME的I期试验，这两个试验都是血管生成抑制剂。