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: 10282058
• 负责人: JAN BEUMER
• 金额: $ 6.27万
• 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/10282058
• 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

本任务单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。该任务订单有一个基期和备选项。