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: 6702702
• 负责人: JOHN G KUHN
• 金额: $ 12.45万
• 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 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6702702
• 关键词: analytical method; antineoplastics; body fluids; central nervous system neoplasms; cerebrospinal fluid; clearance rate; clinical research; clinical trial phase I; clinical trial phase II; clinical trials; excretion; gas chromatography; high performance liquid chromatography; human tissue; method development; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; oral administration; paclitaxel; patient oriented research; pharmacokinetics; temozolomide

DESCRIPTION: (Applicant's Description) For the proposed work, it is our intent as part of the North American Brain Tumor Consortium (NABTC) 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 Program Leader (Michael Prados, M.D. UCSF-Lead Institution). For a pharmacokinetic study, the work will consist of two phases: (a) Development or implementation of a suitable analytical methodology for the measurement of likely tissue and biological fluids. Specifically, HPLC or GC methodologies will be established for quantitation of the compound (such as taxol & temozolomide) being studied. Development of appropriate methodologies may require determination of physicochemical properties such as solubilities, binding of drug to plasma proteins and stability of the drugs in various matrixes at various temperatures. This phase must be successfully completed b e f o r e entering into the next phase. (b) Characterization of the pharmacokinetics/pharmacodynamics of the agent under going clinical evaluation will include: maximum plasma or CSF concentration; plasma or CSF clearance; apparent volume of distribution at steady state; area under the plasma (CSF) time curve; tissue or CSF distribution and harmonic mean plasma/CSF half-lives. Attempts will be made to correlate these pharmacokinetic parameters with the observed biological effects such as toxicity and/or response 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 parent compound.

描述：（申请人的描述） 对于拟议的工作，这是我们作为北美大脑一部分的意图 肿瘤财团（NABTC）以获取有关选定的药理信息 I/II期临床试验中的抗癌剂用于治疗中枢神经系统 恶性肿瘤。 要研究的药物，每项研究的程度将是 由计划负责人（Michael Prados，M.D。UCSF-Lead）决定 机构）。 对于一项药代动力学研究，该工作将由两个 阶段：（a）开发或实施合适的分析 测量可能组织和生物流体的方法。 具体而言，将建立HPLC或GC方法来定量 研究了化合物（例如紫杉醇和替莫唑胺）。 发展 适当的方法可能需要确定物理化学 诸如溶解度，药物与血浆蛋白的结合以及 在各种温度下，药物在各种基质中的稳定性。 这 阶段必须成功完成下一个阶段 阶段。 （b）表征药代动力学/药效学 经过临床评估的代理将包括：最大等离子体或CSF 专注;等离子体或CSF清除；明显的分布量 稳定状态;等离子体（CSF）时间曲线下的面积；组织或CSF 分布和谐波平均等离子体/CSF半衰期。 将尝试 将这些药代动力学参数与观察到的生物学相关 诸如毒性和/或响应数据之类的影响。 通常这些研究将 局限于父母。 但是，在广泛的情况下 发生新陈代谢，开发用于测量的分析方法 将追求代谢物的代谢物 这些化合物的药代动力学/药效学测定可以是 与父院一起进行。