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

项目摘要（请参阅说明）： 用于评估微生物防止艾滋病毒传播能力的体外测定通常利用与抗HIV治疗剂的开发更相关的模型，并使用不敏感的方法在感染后短时间间隔量化病毒产生。为了减轻这些关键生物学测定的缺点，我们开发了微生物传播和灭菌测定法（MTSA），以更敏感，并定量评估在存在微生物化合物的情况下细胞培养中的病毒传播。 MTSA定义了完全抑制病毒在细胞培养中的传播，复制和扩散所需的菌心的浓度，因此可能有助于定义在靶细胞中递送中在配方型微生物剂产物中递送后需要存在的菌心的有效浓度。鉴于量化有效产品所需的微生物产物剂量的难度，重要的是要了解如何与适当的外体和体内药代动力学和药态动力学评估相辅相成，这可能会告知 开发过程并有助于更好地定义适当的剂量策略。在杀生型开发人员中，现在的给药问题是通过哲学来解决