Bioanalytical and Formulation Core

分析、生物统计和制药核心(分析核心C)的总体目标是提供 在直肠杀菌剂灌肠配方和物理方面支持DREAM方案 替诺福韦(TFV)和TFV前药(TFV富马酸二异丙酯[TDF]、TFV丙氨酰胺)的表征 富马酸[TAF]和CMX157)，生物样品定量方法的开发和应用 分析，并对研究数据进行统计分析。核心C的运营围绕着 分析，关于药品配方(药剂学)，药物在生物中的浓度 矩阵(分析)和生成数据的统计解释(生物统计学)。对于生物分析研究， 分析核心C将专注于液相色谱-串联质量的开发和验证 LC-MS/MS法定量测定血浆、直肠液中TFV和TFV前体药 组织。在分析核心C进行的生物制药工作将侧重于开发 TFV灌肠产品即刻配伍方法及质量评价。生物统计学 分析核心C中的专业知识将允许Dream计划使用统计算法来预测TFV 和TFV前药在结肠中的动力学。因此，分析核心C中的每个领域将协同工作，以支持 DREAM计划的临床前和临床项目。分析核心C在以下方面拥有丰富的经验 生物分析、配方开发和生物统计图像分析领域。更进一步，马津克博士 (Analytical Core C Leader)、Rohan(Analytical Core C Co-Leader)和Caffo有着长期的合作 与梦想计划的首席研究员克雷格·亨德里克斯博士。通过提供 TDF、TAF和CMX157的药代动力学数据，核心将直接支持这笔赠款的项目1、2和3 求婚。通过此核心提供的基于公式的工作将帮助项目1、2、3和4以及核心 胡麻B.

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.