Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis
| Autor: | Qianwen Wang, Véronique Dartois, Rada M. Savic, Natasha Strydom, Eric L. Nuermberger, Jacqueline P Ernest, Nan Zhang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Antitubercular Agents Toxicology Bioinformatics Medical and Health Sciences Tuberculosis Multidrug-Resistant Pharmacology & Pharmacy media_common Multidrug-Resistant Biological Sciences simulation Drug Combinations Infectious Diseases Drug development 5.1 Pharmaceuticals 6.1 Pharmaceuticals HIV/AIDS Development of treatments and therapeutic interventions Translational science Infection Drug Tuberculosis translational science media_common.quotation_subject 030106 microbiology Article Vaccine Related 03 medical and health sciences Rare Diseases Disease severity Biodefense medicine Humans pharmacokinetics-pharmacodynamics Pharmacology business.industry Prevention antituberculosis agents Evaluation of treatments and therapeutic interventions modeling medicine.disease drug development 5.9 Resources and infrastructure (treatment development) Multiple drug resistance Regimen Emerging Infectious Diseases Orphan Drug Good Health and Well Being 030104 developmental biology Infectious disease (medical specialty) Antimicrobial Resistance business |
| Zdroj: | Annu Rev Pharmacol Toxicol Annual review of pharmacology and toxicology, vol 61, iss 1 |
| ISSN: | 1545-4304 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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