Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis.
Annu Rev Pharmacol Toxicol
; 61: 495-516, 2021 01 06.
Article
en En
| MEDLINE
| ID: mdl-32806997
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tuberculosis
/
Tuberculosis Resistente a Múltiples Medicamentos
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Annu Rev Pharmacol Toxicol
Año:
2021
Tipo del documento:
Article