期刊
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
卷 61, 期 -, 页码 495-516出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-pharmtox-030920-011143
关键词
pharmacokinetics-pharmacodynamics; drug development; tuberculosis; antituberculosis agents; translational science; modeling; simulation
资金
- Bill and Melinda Gates Foundation
- Critical Path Institute [OPP1174780, OPP1031105-MS05, INV-002483]
- National Institutes of Health Training Grant [T32 GM007175]
- Bill and Melinda Gates Foundation [INV-002483, OPP1174780] Funding Source: Bill and Melinda Gates Foundation
This review discusses the use of translational models and tools in TB drug development, including plasma PK scaling, site-of-disease lesion PK, host-immune and bacteria interplay, combination PK-PD models of multidrug regimens, resistance formation, and integration of data across nonclinical and clinical phases. A proposed workflow integrates these tools with computational platforms to identify drug combinations that can accelerate sterilization, reduce relapse rates, and limit the emergence of resistance.
Tuberculosis (TB) kills more people than any other infectious disease. Challenges for developing better treatments include the complex pathology due to within-host immune dynamics, interpatient variability in disease severity and drug pharmacokinetics-pharmacodynamics (PK-PD), and the growing emergence of resistance. Model-informed drug development using quantitative and translational pharmacology has become increasingly recognized as a method capable of drug prioritization and regimen optimization to efficiently progress compounds through TB drug development phases. In this review, we examine translational models and tools, including plasma PK scaling, site-of-disease lesion PK, host-immune and bacteria interplay, combination PK-PD models of multidrug regimens, resistance formation, and integration of data across nonclinical and clinical phases. We propose a workflow that integrates these tools with computational platforms to identify drug combinations that have the potential to accelerate sterilization, reduce relapse rates, and limit the emergence of resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据