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Second-line antitub...
Second-line antituberculosis drug exposure thresholds predictive of adverse events in multidrug-resistant tuberculosis treatment
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- Wang, Sainan (författare)
- Fudan Univ, Peoples R China
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- Forsman, Lina Davies (författare)
- Karolinska Univ Hosp, Sweden; Karolinska Inst Solna, Sweden
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- Xu, Chunhua (författare)
- Fengxian Dist Ctr Dis Control & Prevent, Peoples R China
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- Zhang, Haoyue (författare)
- Fudan Univ, Peoples R China
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- Zhu, Yue (författare)
- Fudan Univ, Peoples R China
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- Shao, Ge (författare)
- Fudan Univ, Peoples R China
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- Wang, Shanshan (författare)
- Fudan Univ, Peoples R China
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- Cao, Jiayi (författare)
- Fudan Univ, Peoples R China
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- Xiong, Haiyan (författare)
- Fudan Univ, Peoples R China
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- Niward, Katarina (författare)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Infektionskliniken i Östergötland
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- Schön, Thomas (författare)
- Linköpings universitet,Avdelningen för inflammation och infektion,Medicinska fakulteten,Region Östergötland, Klinisk mikrobiologi,Region Östergötland, Infektionskliniken i Östergötland
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- Bruchfeld, Judith (författare)
- Karolinska Institutet,Karolinska Univ Hosp, Sweden; Karolinska Inst Solna, Sweden
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- Zhu, Limei (författare)
- Jiangsu Prov Ctr Dis Control & Prevent, Peoples R China
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- Alffenaar, Jan-Willem (författare)
- Univ Sydney, Australia; Westmead Hosp, Australia; Univ Sydney, Australia
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- Hu, Yi (författare)
- Fudan Univ, Peoples R China
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(creator_code:org_t)
- 2024
- 2024
- Engelska.
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Ingår i: International Journal of Infectious Diseases. - : ELSEVIER SCI LTD. - 1201-9712 .- 1878-3511. ; 140, s. 62-69
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- 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 <middle dot>h/l (bedaquiline M2); 49.3 mg <middle dot>h/l (moxifloxacin); 119.3 mg <middle dot>h/l (linezolid); 718.7 mg <middle dot>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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Nyckelord
- Side effects; Drug exposure; Threshold; Multidrug-resistant tuberculosis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Wang, Sainan
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Forsman, Lina Da ...
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Xu, Chunhua
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Zhang, Haoyue
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Zhu, Yue
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Shao, Ge
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visa fler...
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Wang, Shanshan
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Cao, Jiayi
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Xiong, Haiyan
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Niward, Katarina
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Schön, Thomas
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Bruchfeld, Judit ...
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Zhu, Limei
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Alffenaar, Jan-W ...
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Hu, Yi
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Linköpings universitet
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