Pharmacokinetic Studies with Selected Anticancer Compounds in NSG Mice

选定的抗癌化合物在 NSG 小鼠中的药代动力学研究

• 批准号: 10788022
• 负责人: JOEL REID
• 金额: $ 4.37万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-13 至 2024-09-12
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10788022
• 关键词: Biological Assay; Biological Availability; Blood specimen; Collection; Contractor; Data; Data Analyses; Dose; Drug Kinetics; Exercise; Hemorrhage; Measures; Minor; Modeling; Mus; Performance; Plasma; Procedures; Protocols documentation; Route; Sampling; Schedule; Specific qualifier value; Time; Validation; Vendor; anti-cancer; base; cost; drug-like compound; novel; small molecule

The purpose of this Task Order is to characterize the plasma pharmacokinetics (PK) of small molecule anticancer compounds in mice as outlined below. Rapid turn-around is required. There is a base period and options under this task order. For the base period: 1. Use a standard LC-MS/MS bioanalytical approach for quantification of a small drug-like molecule in mouse plasma. A “generic” assay platform is acceptable and validation to full FDA bioanalytical guidance is not required. An internal standard will be identified and used as a measure of acceptable assay performance. An LLOQ of <10 ng/mL is desirable. 2. It is anticipated that most, if not all, studies will be performed using NSG mice. The NCI will supply the mice for each study to the extent possible, but please include plans for acquisition from an outside vendor should the need arise. 3. Carry out the appended protocol for a mouse PK study with compound(s) that will be provided by the NCI. The protocol specifies 2 (likely unrelated) compounds, 1 route of administration, 8 collection time points for each route, and 3 mice/time point, for a total of 48 plasma samples to be generated for analysis. Appropriate blanks, standards, and QC samples should be included. Novel blood sampling procedures, including micro-bleeds, may be proposed by the offeror. 4. Pharmacokinetic data analysis should include standard non-compartmental modeling to determine Cmax (po), C0 (iv), Tmax, AUC0∞, AUClast, CL, and t½, Vss (or Vd), and %F for each compound to the extent permitted by the data obtained. For Options 1 - 9: 1. For each Option the contractor shall perform PK/bioavailability studies as outlined under “Base Period” for one or two additional compounds per Option. Minor adjustments to the protocol that should not affect cost or schedule (e.g., routes of administration, specific sampling times) may be made. For example, a single route of administration may be used to evaluate two compounds or one compound may be evaluated using two dose levels. Options may be exercised at any time within the Task Order period of performance

本任务指令的目的是描述小分子抗癌化合物在小鼠中的血浆药代动力学（PK），如下所述。需要快速周转。此任务订单下有基期和选项。 基期： 1. 使用标准LC-MS/MS生物分析方法定量测定小鼠血浆中的药物样小分子。“通用”试验平台是可接受的，不需要根据完整的FDA生物分析指南进行验证。 将鉴别内标物，并将其用作可接受测定性能的指标。 理想的LLOQ为<10 ng/mL。 2. 预计大多数（如果不是全部）研究将使用NSG小鼠进行。 NCI将尽可能为每项研究提供小鼠，但如有需要，请纳入从外部供应商处采购的计划。 3. 使用NCI提供的化合物进行小鼠PK研究的随附方案。 方案规定了2种（可能不相关）化合物、1种给药途径、每种途径8个采集时间点和3只小鼠/时间点，共生成48份血浆样品用于分析。应包括适当的空白、标准品和QC样品。要约人可以提出新的血液采样程序，包括微出血。 4. 药代动力学数据分析应包括标准非房室模型，以在获得的数据允许的范围内确定每种化合物的Cmax（po）、C 0（iv）、Tmax、AUC 0 ∞、AUClast、CL和t1/2、Vss（或Vd）和%F。 对于选项1 - 9： 1. 对于每个选项，承包商应按照“基准期”的规定，对每个选项中的一种或两种额外化合物进行PK/生物利用度研究。对方案进行不应影响成本或进度的微小调整（例如，给药途径、具体的取样时间）。 例如，单一给药途径可用于评价两种化合物，或者可使用两种剂量水平评价一种化合物。 购股权可于任务指令履行期内任何时间行使