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: 10625911
• 负责人: JAN BEUMER
• 金额: $ 10.45万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 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/10625911
• 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鼠中小分子核化合物的血浆药代动力学（PK），如下所述。需要快速转弯。此任务订单下有基本期间和选项。 在基本期间： 1。使用标准的LC-MS/MS生物分析方法来定量小鼠血浆中的小药物样分子。 “通用”测定平台是可以接受的，并且不需要对完整的FDA生物分析指导进行验证。内标将被识别并用作可接受测定性能的量度。 <10 ng/ml的LLOQ是可取的。 2。预计将使用NSG小鼠进行大多数（如果不是全部）研究。 NCI将在可能的范围内为每项研究提供小鼠，但请在需要时包括外部供应商的收购计划。 3。执行NCI提供的化合物的鼠标PK研究协议。该协议指定2（可能是无关的）化合物，1个给药途径，每条路线的8个收集时间点和3个鼠标/时间点，总共生成48个血浆样本进行分析。应包括适当的空白，标准和QC样品。报价可能会提出包括微观流血在内的新型血液采样程序。 4。药代动力学数据分析应包括标准的非室内建模，以确定CMAX（PO），C0（iv），TMAX，AUC0-∞，Auclast，cl和T½，VSS（或VD）和％F，每种化合物在获得的数据允许的范围内得到了每种化合物的范围。 对于选项1-9： 1。对于每种选择，承包商应在“基本周期”下对每种选项的另一种或两种额外的化合物进行PK/生物利用度研究。可以对不应影响成本或时间表的协议进行少量调整（例如，管理途径，特定的采样时间）。例如，可以使用单个给药途径来评估两种化合物，或者可以使用两个剂量水平评估一种化合物。可以在绩效任务订单期内任何时间行使选项