Determination of Dosing Concentrations of Formulated APIs using the MTSA

使用 MTSA 确定配方 API 的剂量浓度

• 批准号: 8404125
• 负责人: Robert Walter Buckheit
• 金额: $ 33.75万
• 依托单位: IMQUEST BIOSCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-06-22 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8404125
• 关键词: Address; Algorithms; Biological Assay; CCR5 gene; Cell Culture Techniques; Cells; Clinical; Coitus; Complement; Development; Dose; Drug Kinetics; Epithelial; Evaluation; Event; HIV; HIV vaccine; HIV-1; Immune; In Vitro; Infection; Instruction; Laboratories; Light; Local Microbicides; Methodology; Modeling; Mucous Membrane; Pharmaceutical Preparations; Pharmacodynamics; Philosophy; Process; Production; Rectum; Research; Reverse Transcription; Sterilization; Therapeutic Agents; Thinking; Tissues; Vagina; Virus; Virus Replication; assay development; base; in vitro Assay; in vivo; microbicide; monocyte; novel; prevent; time interval; transmission process

PROJECT SUMMARY (See instructions): In vitro assays used to evaluate the ability of a microbicide to prevent HIV transmission typically utilize models more relevant to the development of anti-HIV therapeutic agents and quantify virus production at short time intervals following infection (3-6 days) using insensitive methodology. To mitigate the shortcomings of these critical biological assays, we have developed a microbicide transmission and sterilization assay (MTSA) to more sensitively and quantitatively evaluate virus transmission in cell culture in the presence of microbicidal compounds. The MTSA defines the concentration of the microbicide required to totally suppress the transmission, replication, and spread of virus in cell culture and may thus help define the effective concentration of the microbicide required to be present in target cells upon delivery in a formulated microbicide product. In light of the difficulty of quantifying the dose of a microbicide product that is required for the delivery of an effective product, it is important to understand how in vitro methodology, complemented with appropriate ex vivo and in vivo pharmacokinetic and pharmacodynamics evaluations, might inform the development process and serve to better define appropriate dosing strategies. Among microbicide developers, the dosing problem is now addressed through the philosophy of

项目概述（见说明）：