CANCER & AIDS DRUGS--PRECLIN PHARMACOL/TOXICOLOGY

该合同的目的是获得药理学和 用于治疗癌症的新药的毒理学数据和 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以研究人类临床 审判 这些数据是在一系列毒理学和 药理学研究，包括以下内容： 分析阶段：药物鉴别分析（例如，IR、NMR、MP、MS等） NCI提供的剂量浓度程序验证 药物含量测定所需方法的分析和验证 将在收到药物后立即启动。 药代动力学阶段：将测定血浆消除动力学 单次静脉给药后，犬和啮齿类动物中可能存在。 非胃肠外途径的生物利用度和血浆清除率将 以确定产生所需的剂量 血浆中的有效药物浓度，用于未来的毒性研究。 的 抗艾滋病药物穿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，有必要 确定最大耐受剂量（MTD）和剂量限制性毒性 (DLT)在比格犬和啮齿类动物中。 INDA指导的毒性阶段：对于每种药物，有必要 确定与药物血浆浓度相关毒性和安全性 或曲线下面积。 在初步毒性阶段和INDA指导毒性阶段， 可能需要使用灵长类动物作为替代物种， 罕见的基础。

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.