A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis
Conclusion: The framework we developed requires limited drug- and species-specific information to reconstruct accurate PK dynamics, delivering a unified viewpoint on anti-TB drug distribution at the site-of-action and a flexible fit-for-purpose tool to accelerate model-informed drug design pipelines and facilitate translation into the clinic. (Source: Frontiers in Pharmacology)
Source: Frontiers in Pharmacology - January 4, 2024 Category: Drugs & Pharmacology Source Type: research
Second-line anti-tuberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment
Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem [1]. The introduction of new (bedaquiline) and repurposed drugs (linezolid and clofazimine) is expected to improve treatment outcomes [2], but adverse events (AEs) related to these drugs have been frequently reported during the long-term MDR-TB treatment [3]. As many as 8.4% of patients with MDR-TB experienced serious AEs, including corrected QT interval by Fridericia's formula (QTcF) above 500ms, bone marrow suppression, peripheral neuropathy, and kidney/liver failure, resulting in treatment failure, as well as major morbidity and even death [...
Source: International Journal of Infectious Diseases - January 2, 2024 Category: Infectious Diseases Authors: Sainan Wang, Lina Davies Forsman, Chunhua Xu, Haoyue Zhang, Yue Zhu, Ge Shao, Shanshan Wang, Jiayi Cao, Haiyan Xiong, Katarina Niward, Thomas Sch ön, Judith Bruchfeld, Limei Zhu, Jan-Willem Alffenaar, Yi Hu Source Type: research
Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment
Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem [1]. The introduction of new (bedaquiline) and repurposed drugs (linezolid and clofazimine) is expected to improve treatment outcomes [2], but adverse events (AEs) related to these drugs have been frequently reported during the long-term MDR-TB treatment [3]. As many as 8.4% of patients with MDR-TB experienced serious AEs, including corrected QT interval by Fridericia's formula (QTcF) above 500 ms, bone marrow suppression, peripheral neuropathy, and kidney/liver failure, resulting in treatment failure, as well as major morbidity and even death ...
Source: International Journal of Infectious Diseases - January 2, 2024 Category: Infectious Diseases Authors: Sainan Wang, Lina Davies Forsman, Chunhua Xu, Haoyue Zhang, Yue Zhu, Ge Shao, Shanshan Wang, Jiayi Cao, Haiyan Xiong, Katarina Niward, Thomas Sch ön, Judith Bruchfeld, Limei Zhu, Jan-Willem Alffenaar, Yi Hu Source Type: research
Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis
ConclusionsBedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies. (Source: Journal of Antimicrobial Chemotherapy)
Source: Journal of Antimicrobial Chemotherapy - December 22, 2023 Category: Microbiology Source Type: research
Bioactives from medicinal herb against bedaquiline resistant tuberculosis: Removing the Dark Clouds from the Horizon
In this study, we have taken the benzylisoquinoline alkaloids from thalictrum foliolosum due to its antimicrobial activity reported in prior literature. We used an efficient and optimized structure-based strategy to examine the wild type (WT) and mutated protein upon molecule binding. Our results emphasize the drastic decline in BQ binding affinity of mutant and WT atpE subunit-c complexes compared to thalirugidine (top hit) from thalictrum foliolosum. The decrease in BQ binding free energy is due to electrostatic energy because nearly every atom in a macromolecule harbors a partial charge, and molecules taking part in mol...
Source: Cell Research - December 21, 2023 Category: Cytology Authors: Rahul Singh Souvik Manna Hemraj Nandanwar Rituraj Purohit Source Type: research
