CANCER & AIDS DRUGS--PRECLIN PHARMACOL/TOXICOLOGY

癌症

• 批准号: 2300656
• 负责人: J PAGE
• 金额: $ 138.83万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 1995-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2300656
• 关键词: CANCER; AIDS; DRUGS; PRECLIN; PHARMACOL

The objective of this contract is to acquire pharmacologic and toxicologic data on new drugs for the treatment of Cancer and the Acquired Immunodeficiency Syndrome (AIDS). The data will serve as the basis of the Government's filing for an INDA to institute human clinical trials. This data is collected in a series of toxicology and pharmacology studies and consists of the following: * Analytical Phase: Drug identity analysis (e.g., IR, NMR, MP, MS, etc.) validation of the procedures supplied by the NCI for dose concentration analyses and validation of the requisite methodology for assay of drug in biological fluids will be initiated immediately upon receipt of drug. * Pharmacokinetic Phase: Plasma elimination kinetics will be determined in dogs and possibly in rodents after single intravenous doses of drug. Bioavailability of non-parenteral routes and plasma clearance rates will be determined in order to establish the dose required to produce effective drug concentrations in plasma for future toxicity studies. The ability of an anti-AIDS drug to cross the blood-brain barrier will also be assessed in dogs and possibly rodents. * Preliminary Toxicity Phase: For each drug, it will be necessary to establish a maximum tolerated dose (MTD) and dose limiting toxicities (DLT) in both beagle dogs and rodents. * INDA-Directed Toxicity Phase: For each drug, it will be necessary to establish toxicity and safety in relation to drug plasma concentrations or area-under-the-curve in both beagle dogs and rodents. In the Preliminary Toxicity Phase and the INDA-Directed Toxicity Phase, the use of primates as an alternative species may be required on an infrequent basis.

这份合同的目标是获得药理和 治疗癌症新药的毒理学数据及其临床意义 获得性免疫缺陷综合症(艾滋病)。这些数据将作为 政府申请INDA建立人类临床研究所的依据 审判。这些数据被收集在一系列毒物学和 药理学研究并包括以下内容： *分析阶段：药物鉴定分析(如IR、核磁共振、MP、MS等) NCI提供的剂量浓度程序的验证 药物检测所需方法学的分析与验证 将在收到药物后立即启动生物液中的。 *药代动力学阶段：将确定血浆消除动力学 在狗身上，也可能在啮齿动物身上，在单次静脉注射药物后。 非肠外途径的生物利用度和血浆清除率将 以确定生产所需的剂量 血浆中的有效药物浓度，用于未来的毒性研究。这个 抗艾滋病药物通过血脑屏障的能力也将 在狗和可能的啮齿动物身上进行评估。 *初步毒性阶段：对于每种药物，将需要 建立最大耐受剂量(MTD)和剂量限制毒性 (DLT)在比格犬和啮齿动物中。 *INDA指示的毒性阶段：对于每种药物，必须 建立与药物血药浓度相关的毒性和安全性 或者比格犬和啮齿类动物的曲线下面积。 在初步毒性阶段和INDA定向毒性阶段， 使用灵长类动物作为替代物种可能需要在 不常见的基础。