Please use this identifier to cite or link to this item:
https://wslhd.intersearch.com.au/wslhdjspui/handle/1/9014
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Wang, S. | - |
dc.contributor.author | Forsman, L. D. | - |
dc.contributor.author | Xu, C. | - |
dc.contributor.author | Zhang, H. | - |
dc.contributor.author | Zhu, Y. | - |
dc.contributor.author | Shao, G. | - |
dc.contributor.author | Wang, S. | - |
dc.contributor.author | Cao, J. | - |
dc.contributor.author | Xiong, H. | - |
dc.contributor.author | Niward, K. | - |
dc.contributor.author | Schon, T. | - |
dc.contributor.author | Bruchfeld, J. | - |
dc.contributor.author | Zhu, L. | - |
dc.contributor.author | Alffenaar, Jan-Willem C. | - |
dc.contributor.author | Hu, Y. | - |
dc.date.accessioned | 2024-03-11T00:58:03Z | - |
dc.date.available | 2024-03-11T00:58:03Z | - |
dc.date.issued | 2024 | - |
dc.identifier.citation | International Journal of Infectious Diseases 140:62-69, 2024 | - |
dc.identifier.uri | https://wslhd.intersearch.com.au/wslhdjspui/handle/1/9014 | - |
dc.description.abstract | OBJECTIVES: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds.METHODS: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. RESULTS: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg.h/l (bedaquiline M2); 49.3 mg.h/l (moxifloxacin); 119.3 mg.h/l (linezolid); 718.7 mg.h/l (cycloserine). CONCLUSIONS: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs. Copyright 2024. Published by Elsevier Ltd. | - |
dc.title | Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment | - |
dc.type | Journal Article | - |
dc.identifier.doi | https://dx.doi.org/10.1016/j.ijid.2024.01.001 | - |
dc.subject.keywords | Antitubercular Agents | - |
dc.subject.keywords | Cycloserine | - |
dc.subject.keywords | Diarylquinolines | - |
dc.subject.keywords | Linezolid | - |
dc.subject.keywords | Moxifloxacin | - |
dc.subject.keywords | Tuberculosis, Multidrug-Resistant | - |
dc.identifier.journaltitle | International Journal of Infectious Diseases | - |
dc.identifier.department | Pharmacy | - |
dc.contributor.wslhd | Alffenaar, Jan-Willem C. | - |
dc.type.studyortrial | Multicenter Study | - |
dc.type.studyortrial | Observational Study | - |
dc.identifier.pmid | 38176643 | - |
dc.identifier.facility | Westmead | - |
Appears in Collections: | Westmead Hospital 2019 - 2024 |
Files in This Item:
There are no files associated with this item.
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.