| Autor: |
Sainan Wang, Lina Davies Forsman, Chunhua Xu, Haoyue Zhang, Yue Zhu, Ge Shao, Shanshan Wang, Jiayi Cao, Haiyan Xiong, Katarina Niward, Thomas Schön, Judith Bruchfeld, Limei Zhu, Jan-Willem Alffenaar, Yi Hu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
International Journal of Infectious Diseases, Vol 140, Iss , Pp 62-69 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1201-9712 |
| DOI: |
10.1016/j.ijid.2024.01.001 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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