Preclinical Toxicology and Pharmacology of Drugs for Cancer

该合同的目的是获得用于治疗癌症和其他疾病（包括孤儿病）的新药候选物的药理学和毒理学数据。具有诊断和监测肿瘤进展潜力的癌症显像剂也使用该合同进行评估。这些数据作为研究性新药（IND）申请的一部分定期提交给FDA，因此将符合所有FDA指南。本合同的工作范围包括： a）验证用于剂量浓度分析和用于测定生物液体中候选药物浓度的分析方法。 B）在啮齿动物和非啮齿动物物种中进行药代动力学研究，以确定血浆消除动力学。确定非胃肠外途径的生物利用度和血浆清除率，以确定在血浆中产生有效浓度所需的剂量，并将信息应用于设计候选药物特定毒理学研究。 c）进行初步毒理学研究，以确定候选药物在啮齿动物和非啮齿动物物种中的相对毒性和潜在的剂量限制毒性。 d）进行确定性毒理学研究，以确定与候选药物暴露相关的毒性和安全性（血浆浓度或药物浓度-时间曲线下面积）。根据FDA的要求，这些研究在啮齿动物和非啮齿动物种属中进行。研究是为被评价的候选药物定制的，例如指定给药途径和时间表，包括一般毒性/安全性测定，但可能包括专门的评价，例如心血管毒性、神经毒性、免疫毒性、肺毒性或生殖/畸形学效应。 e）进行体外研究，如致突变性和骨髓试验。

The objective of this contract is to acquire pharmacologic and toxicologic data on new drug candidates for the treatment of cancer and other diseases, including orphan diseases. Cancer imaging agents with the potential for diagnosing and monitoring tumor progression are evaluated using this contract as well. These data are routinely submitted to the FDA as part of an investigational new drug (IND) application and as such will conform with all FDA Guidances. The work scope for this contract includes: a) Validation of analytical procedures for dose concentration analyses and for assaying drug candidate concentrations in biological fluids. b) Conduct pharmacokinetic studies in rodent and non-rodent species to determine plasma elimination kinetics. Determine bioavailability of non-parenteral routes and plasma clearance rates in order to establish the dose required to produce effective concentrations in plasma and apply the information to design drug candidate-specific toxicology studies. c) Conduct preliminary toxicology studies to establish relative toxicity of the drug candidate in rodent and non-rodent species and potential dose limiting toxicities. d) Conduct definitive toxicology studies to establish toxicity and safety in relation to drug candidate exposure (plasma concentration or area under the drug concentration versus time curve). These studies are performed in rodent and non-rodent species, as required by the FDA. Studies are customized for the drug candidate being evaluated, such as specifying the route and schedule of administration and include general toxicity/safety determinations, but may include specialized evaluations such as cardiovascular toxicity, neurotoxicity, immunotoxicity, pulmonary toxicity, or reproductive/teratology effects. e) Conduct in vitro studies such as mutagenicity and bone marrow assays.