Development of Pharmacokinetic Models to Characterize the Disposition of New Ant

开发表征新蚂蚁处置的药代动力学模型

• 批准号: 6433351
• 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/6433351
• 关键词: antineoplastics; blood proteins; butyrates; camptothecin; chemical binding; cis platinum compound; clinical research; clinical trial phase I; drug screening /evaluation; human subject; human therapy evaluation; immunoconjugates; model; model design /development; neoplasm /cancer chemotherapy; paclitaxel; 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 Section (CPS) has as its primary interest the use of pharmacokinetic and pharmacodynamic concepts in the development of novel anticancer agents. The CPS is directly responsible for the pharmacokinetic/pharmacodynamic analysis of numerous Phase I and II clinical trials conducted within the NCI. In addition, the CPS 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 CPS 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, depsipeptide, docetaxel, perifosine, and paclitaxel. Currently, we are characterizing the pharmacokinetics of multiple day dosing of PSC 833 when administered with vinblastine and paclitaxel. This is an attempt to characterize any interactions between PSC 833 and either of these agents both in the clinical pharmacokinetic data, as well as through in vitro metabolism studies. Recently, we have completed a Phase I trial of COL-3, a matrix metalloproteinase inhibitor. We are initiating a Phase I trial 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。临床药理学科（CPS）在新型抗癌剂的发展中使用药代动力学和药效学概念的主要兴趣。 CP直接负责NCI内进行的许多I和II期临床试验的药代动力学/药效分析。此外，CPS为壁外社区其他地方进行的许多研究提供了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）。 The drugs with which the CPS 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,沙利度胺，9AC，腹膜内顺铂，腹膜内carboplatin，depsipeptide，多西他赛，perifosine和紫杉醇。目前，我们正在用Vinblastine和Paclitaxel给药时，表征了PSC 833多天给药的药代动力学。这是为了表征PSC 833与临床药代动力学数据中这些药物中的任何一种之间的任何相互作用，以及通过体外代谢研究。最近，我们完成了Col-3（基质金属蛋白酶抑制剂）的I期试验。我们正在启动CC5013和2ME的I期试验，这两个试验都是血管生成抑制剂。