Phase I/II PK/PD Studies of Agents for CNS Malignancies*

CNS 恶性肿瘤药物的 I/II 期 PK/PD 研究*

• 批准号: 6927984
• 负责人: JOHN G KUHN
• 金额: $ 18.09万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-03-28 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927984
• 关键词: analytical method; antineoplastics; body fluids; central nervous system neoplasms; cerebrospinal fluid; clearance rate; clinical research; clinical trials; cooperative study; excretion; gas chromatography; high performance liquid chromatography; human tissue; method development; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; oral administration; pharmacokinetics

DESCRIPTION (provided by applicant): For the proposed Pharmacokinetic Center, it is our intent as part of the North American Brain Tumor Consortium (NABTC, Central Operations Office) to derive pharmacological information on selected anticancer agents in phase I/II clinical trials for the treatment of CNS malignancies. The drugs to be studied and the extent of each study will be determined by the Group Leader (Michael Prados, M.D., UCSF). For the pharmacokinetic studies, the work will consist of four phases: (a) Design of an appropriate pharmacokinetic sampling procedure for inclusion in the NABTC protocol. (b) Develop or implement a suitable analytical method for the measurement of likely tissue and biological fluids. Specifically, HPLC or LC/MS validated methodologies will be established for real time quantitation of the compound (such as CCI-779 & ZD1839) being studied. (c) Provision of the pharmacokinetic parameters including maximum plasma or tissue concentration; plasma or clearance; apparent volume of distribution at steady state; area under the plasma time curve; tissue distribution and harmonic mean plasma half-lives. Attempts will be made to correlate these pharmacokinetic parameters with the observed biological effects such as toxicity, response or biological surrogate marker data. Generally these studies will be confined to the parent drug. However, in instances where extensive metabolism occurs, the development of analytical methodology for measurement of the metabolites will be pursued so that parallel pharmacokinetic/pharmacodynamic determinations of these compounds can be conducted along with the apparent compound.

描述（由申请人提供）：对于拟议的药代动力学中心，我们的目的是作为北美脑肿瘤财团（NABTC，中央运营办公室）的一部分，以在I/II期临床试验中获取有关CNS恶性肿瘤治疗的I/II临床试验中选定抗癌药物的药理信息。要研究的药物和每项研究的程度将由小组领导者（Michael Prados，M.D。，UCSF）确定。对于药代动力学研究，这项工作将包括四个阶段：（a）设计适当的药代动力学抽样程序，以纳入NABTC方案。 （b）开发或实施一种适当的分析方法，用于测量可能的组织和生物流体。具体而言，将建立HPLC或LC/MS验证的方法，用于研究该化合物的实时定量（例如CCI-779＆ZD1839）。 （c）提供药代动力学参数，包括最大血浆或组织浓度；血浆或清除；在稳态下的明显分布量；血浆时间曲线下方的区域；组织分布和谐波平均血浆半衰期。将尝试将这些药代动力学参数与观察到的生物学作用（例如毒性，反应或生物替代标记数据）相关联。通常，这些研究将局限于母体药物。但是，在发生广泛代谢的情况下，将采用分析方法来测量代谢物，以便可以对这些化合物的平行药代动力学/药物学测定以及明显的化合物进行。