Bioanalytical and Formulation Core

生物分析和制剂核心

• 批准号: 8889594
• 负责人: Mark A Marzinke
• 金额: $ 43.87万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8889594
• 关键词: Address; Adherence; Algorithms; Applications Grants; Area; Attributes of Chemicals; Biological; Biological Products; Clinical; Clinical Research; Clinical Trials; Collaborations; Collection; Colon; Colorectal; Data; Data Analyses; Data Reporting; Data Storage and Retrieval; Development; Drug Formulations; Drug Kinetics; Elements; Ensure; Ethics; Evaluation; Excipients; Fumarates; Gel; Generations; Goals; HIV; Human; Image; Image Analysis; Kinetics; Laboratories; Liquid substance; Measurement; Methods; Modeling; Parents; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacy (field); Pharmacy facility; Plasma; Preparation; Principal Investigator; Procedures; Process; Prodrugs; Prophylactic treatment; Protocols documentation; Radiolabeled; Reporting; Reproducibility; Sampling; Sampling Studies; Series; Site; Statistical Algorithm; Structure; Tenofovir; Tenofovir disoproxil fumarate; Testing; Tissues; Validation; Work; base; clinical research site; enema administration; experience; microbicide; novel; operation; pre-clinical; product development; programs; quality assurance; radiotracer; rectal; rectal microbicide; stability testing

The overall goal of the Analytical, Biostatistical and Pharmaceutics Core (Analytical Core C) is to provide support to the DREAM Program with respect to rectal microbicide enema formulation and physical characterization for tenofovir (TFV) and TFV prodrugs (TFV disoproxil fumarate [TDF], TFV alafenamide fumarate [TAF], and CMX157), development and application of quantitative methods for biological sample analysis, and statistical analysis of study data. The operations of Core C focus around the central idea of analysis, with regards to pharmaceutical product formulation (pharmaceutics), drug concentration in biological matrices (analytical), and statistical interpretation of generated data (biostatistical). For bioanalytical studies, Analytical Core C will focus on the development and validation of liquid chromatographic-tandem mass spectrometric (LC-MS/MS) methods for the quantification of TFV and TFV prodrugs in plasma, rectal fluid, and tissue. Biopharmaceutical work conducted in Analytical Core C will focus on the development of extemporaneous compounding methods and quality assessments for TFV enema products. The Biostatistical expertise within Analytical Core C will allow the DREAM program to use statistical algorithms to project TFV and TFV prodrug kinetics in the colon. Thus, each area within Analytical Core C will work in tandem to support the pre-clinical and clinical projects of the DREAM program. Analytical Core C has significant experience in the areas of bioanalysis, formulation development, and biostatistical image analysis. Further, Drs. Marzinke (Analytical Core C Leader), Rohan (Analytical Core C Co-Leader) and Caffo have long-standing collaborations with Dr. Craig Hendrix, the principal investigator of the DREAM program. Through the provision of pharmacokinetic data on TDF, TAF, and CMX157, the core will directly support Projects 1, 2 and 3 of this grant proposal. Formulation based efforts provided through this Core will assist Projects 1, 2, 3, & 4 as well as Core B.

分析、生物统计和药学核心（分析核心C）的总体目标是提供 在直肠杀微生物剂灌肠剂配方和物理治疗方面支持DREAM计划 替诺福韦（TFV）和TFV前药（TFV富马酸二异丙酯[TDF]、TFV艾拉酚胺）的表征 富马酸盐[TAF]和CMX 157），生物样品定量方法的开发和应用 分析和研究数据的统计分析。核心C的操作集中在以下中心思想上： 分析，关于药品配方（药剂学），生物制剂中的药物浓度 矩阵（分析）和生成数据的统计解释（生物统计）。对于生物分析研究， 分析核心C将侧重于液相色谱-串联质谱的开发和验证 用于定量血浆、直肠液中TFV和TFV前药的光谱（LC-MS/MS）方法， 组织.在分析核心C中进行的生物制药工作将侧重于开发 临时配制方法和TFV灌肠剂产品的质量评估。生物统计 分析核心C中的专业知识将使梦想计划能够使用统计算法来预测TFV 和结肠中的TFV前药动力学。因此，分析核心C中的每个领域将协同工作， 梦想计划的临床前和临床项目。分析核心C在以下方面具有丰富的经验： 生物分析、制剂开发和生物统计图像分析领域。此外，Marzinke博士 （分析核心C负责人）、罗汉（分析核心C联合负责人）和Caffo有着长期的合作关系 克雷格亨德里克斯博士，梦想计划的首席研究员。通过提供 TDF、TAF和CMX 157的药代动力学数据，核心将直接支持本基金的项目1、2和3。 提议通过该核心提供的基于制定的工作将有助于项目1、2、3和4以及核心 B。