PRECLINICAL PHARMACOLOGY OF CANCER & AIDS DRUGS

癌症临床前药理学

• 批准号: 2792711
• 负责人: NANCY A. TURNER
• 金额: $ 27.9万
• 依托单位: BATTELLE MEMORIAL INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-12-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2792711
• 关键词: analytical chemistry; antiAIDS agent; antineoplastics; clearance rate; clinical chemistry; dogs; dosage; drug administration rate /duration; drug administration routes; drug classification; drug screening /evaluation; histopathology; laboratory mouse; laboratory rat; pharmacokinetics; postmortem

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.

该合同的目的是获取药理学和 有关癌症和治疗新药的毒理学数据 获得的免疫缺陷综合征（AIDS）。 数据将作为 政府申请INDA建立人类临床的基础 试验。 这些数据收集在一系列毒理学和 药理学研究和以下内容： *分析阶段：药物身份分析（例如，IR，NMR，MP，MS等） 验证NCI为剂量浓度提供的程序 分析和验证药物测定的必要方法 在收到药物后，将立即开始生物流体。 *药代动力学阶段：将确定血浆消除动力学 单次静脉注射药物后，在狗中，可能是啮齿动物中的啮齿动物。 非少年路线和血浆清除率的生物利用度将 确定以建立生产所需的剂量 血浆中有效的药物浓度用于未来的毒性研究。 这 抗AIDS药物越过血脑屏障的能力也将 在狗和可能的啮齿动物中进行评估。 *初步毒性阶段：对于每种药物，都必须 建立最大耐受剂量（MTD）和剂量限制毒性 （DLT）在小猎犬和啮齿动物中。 * INDA定向的毒性阶段：对于每种药物，都必须 建立与药物血浆浓度有关的毒性和安全性 或小猎犬犬和啮齿动物的弯曲区域。 在初步毒性阶段和INDA定向毒性阶段， 可能需要使用灵长类动物作为替代物种 罕见的基础。