Using Clinical Pharmacology Principals in the Developmen

一个成功的药物开发计划需要对被评估药物的临床药理学有全面的了解。临床药理学研究核心(CPRC)主要关注药代动力学和药效学概念在新型抗癌药物开发中的应用。CPRC直接负责NCI内进行的许多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。在这一节中，我们使用分隔和非分隔的方法来定义代理的处置。此外，我们经常需要通过体外技术来表征新制剂的血浆蛋白结合特性和新陈代谢。我们的几个临床试验使用了带有反馈机制的自适应控制来针对特定的血浆浓度(例如苏拉明、CAI)。CPRC最有经验的药物包括：苏拉明、苯乙酸酯、苯丁酸酯、TNP-470、PMEA、AZT、PSC 833、CAI、DAB486IL2、Ig G-RFB4-SMPT-DGA CD22、Ig G-HD37-SMPT-DGA CD19、奥马铂、UCN-01、黄匹利多、沙利度胺、9AC、顺铂、卡铂、多西紫杉醇和紫杉醇。目前，我们正在研究酮康唑和多西紫杉醇之间的相互作用，并了解MS275、周福辛和地塞米松的药代动力学。我们目前正在进行CC5013和2Me的I期试验，这两种药物都是血管生成抑制剂。

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.