Pharmacokinetics and Bioanalysis Core

药代动力学和生物分析核心

• 批准号: 9282496
• 负责人: Camilo Rojas
• 金额: $ 12.17万
• 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/9282496
• 关键词: Adverse effects; Anti-Retroviral Agents; Attenuated; Behavioral; Blood Glucose; Brain; Cerebrospinal Fluid; Clinical; Clinical Research; Cognitive; Cognitive deficits; Dependence; Dose; Drug Exposure; Drug Interactions; Drug Kinetics; Energy Metabolism; Ensure; Enzyme-Linked Immunosorbent Assay; Exhibits; Exposure to; Glucose; HIV Infections; HIV therapy; HIV-associated neurocognitive disorder; Hand functions; Histologic; Human; Impaired cognition; Infection; Insulin; Lipids; Measurement; Methods; Modeling; Monitor; Morphology; Mus; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Plasma; Regimen; Sampling; Scientist; Specimen; Work; brain tissue; efficacy study; experience; lipid metabolism; liquid chromatography mass spectrometry; mouse model; peripheral blood; pharmacodynamic model; pre-clinical; preclinical study; response; virology

PROJECT SUMMARY (Pharmacokinetics and Bioanalysis Core) The Pharmacokinetics and Bioanalysis core will support both the preclinical and clinical studies. It will conduct the pharmacokinetic analyses of insulin in plasma, cerebrospinal (CSF) and brain tissue in the EcoHIV mouse model. It will also determine levels of antiretroviral (ARV) drugs and glucose levels in plasma, CSF, and brain tissue. In conjunction with the pharmacological results obtained in the EcoHIV model, the core will establish a pharmacokinetic/pharmacodynamic (PK/PD) model relating drug exposures to positive efficacy endpoints. Results from the mouse model will also inform on potential side effects of insulin brain exposure, interaction between insulin and ARV administration, and aide in the choice of CSF markers to follow insulin efficacy in humans. The core will support the clinical studies with bioanalyses of insulin and glucose in CSF and plasma as well as evaluate ARV drugs in plasma from clinical studies to ensure insulin does not alter ARV disposition. Core scientists have extensive experience with pharmacokinetics and bioanalysis including the specific measurements mentioned above.

项目总结（药代动力学和生物分析核心） 药代动力学和生物分析核心将支持临床前和临床研究。它将进行 EcoHIV小鼠血浆、脑脊液（CSF）和脑组织中胰岛素的药代动力学分析 模型它还将确定抗逆转录病毒（ARV）药物的水平和血浆，CSF和大脑中的葡萄糖水平 组织.结合EcoHIV模型中获得的药理学结果，核心将建立一个 药代动力学/药效学（PK/PD）模型将药物暴露与阳性疗效终点联系起来。 来自小鼠模型的结果还将告知胰岛素脑暴露的潜在副作用， 胰岛素和ARV给药之间的关系，并帮助选择CSF标志物，以跟踪胰岛素在 人类核心将通过CSF和血浆中胰岛素和葡萄糖的生物分析支持临床研究 以及从临床研究中评估血浆中的抗逆转录病毒药物，以确保胰岛素不会改变抗逆转录病毒药物的分布。 核心科学家在药代动力学和生物分析方面拥有丰富的经验，包括特定的 上面提到的测量。