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: 10625910
• 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/10625910
• 关键词: Biological Assay; Biological Availability; Blood specimen; Collection; Contractor; Data; Data Analyses; Dose; Drug Kinetics; Exercise; Measures; Minor; Modeling; Mus; Performance; Pharmaceutical Preparations; Plasma; Procedures; Protocols documentation; Route; Sampling; Schedule; Specific qualifier value; Time; Validation; Vendor; anti-cancer; base; cost; 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

该任务顺序的目的是表征小分子抗癌化合物在小鼠体内的血浆药代动力学(PK)，如下所述。需要迅速扭转局面。此任务订单下有一个基准期和选项。 对于基期： 1.使用标准LC-MS/MS生物分析方法对小鼠血浆中的小分子类药物进行定量。“通用”化验平台是可以接受的，不需要对FDA完整的生物分析指南进行验证。将确定一个内部标准，并将其用作可接受的分析性能的衡量标准。LLOQ为&lt；10 ng/mL是理想的。 2.预计大多数研究(如果不是全部的话)将使用NSG小鼠进行。NCI将在可能的范围内为每项研究提供MICE，但如果需要，请包括从外部供应商采购的计划。 3.使用化合物(S)进行小鼠PK研究的附加方案，该方案将由NCI提供。该方案指定了2种(可能无关)化合物、1种给药途径、每种途径8个采集时间点和3个小鼠/时间点，总共产生48个血浆样本进行分析。应包括适当的空白、标准和质量控制样品。新的血液采样程序，包括微量出血，可以由出资人提出。 4.药代动力学数据分析应包括标准的非室模型，以在所获得的数据允许的范围内确定每种化合物的Cmax(Po)、C0(Iv)、Tmax、AUC0∞、AUClast、CL和tü、Vss(或Vd)和%F。 对于选项1-9： 1.对于每个备选方案，承包商应对每个备选方案进行“基准期”中概述的一种或两种额外化合物的PK/生物利用度研究。可对协议进行不应影响成本或进度的微小调整(例如，给药路线、特定采样时间)。例如，一种给药途径可以用来评价两种化合物，或者一种化合物可以用两个剂量水平来评价。可在任务单履行期内随时行使选择权