{"title":"非结核分枝杆菌肺病治疗中氯苯嗪的血清浓度和安全性/有效性","authors":"Fumiya Watanabe , Keiji Fujiwara , Koji Furuuchi , Masashi Ito , Kazuhiko Hanada , Tatsuya Kodama , Akio Aono , Satoshi Mitarai , Takashi Yoshiyama , Atsuyuki Kurashima , Ken Ohta , Kozo Morimoto","doi":"10.1016/j.rmed.2024.107718","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Clofazimine (CFZ) has shown promising effects against <em>Mycobacterium avium</em>-<em>intracellulare</em> complex pulmonary disease (MAC-PD) and <em>Mycobacterium abscessus</em> species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD.</p></div><div><h3>Methods</h3><p>This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's <em>t</em>-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included.</p></div><div><h3>Results</h3><p>The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (<em>P</em> < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9–25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3–38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study.</p></div><div><h3>Conclusion</h3><p>CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.</p></div>","PeriodicalId":21057,"journal":{"name":"Respiratory medicine","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment\",\"authors\":\"Fumiya Watanabe , Keiji Fujiwara , Koji Furuuchi , Masashi Ito , Kazuhiko Hanada , Tatsuya Kodama , Akio Aono , Satoshi Mitarai , Takashi Yoshiyama , Atsuyuki Kurashima , Ken Ohta , Kozo Morimoto\",\"doi\":\"10.1016/j.rmed.2024.107718\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Clofazimine (CFZ) has shown promising effects against <em>Mycobacterium avium</em>-<em>intracellulare</em> complex pulmonary disease (MAC-PD) and <em>Mycobacterium abscessus</em> species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD.</p></div><div><h3>Methods</h3><p>This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's <em>t</em>-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included.</p></div><div><h3>Results</h3><p>The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (<em>P</em> < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9–25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3–38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study.</p></div><div><h3>Conclusion</h3><p>CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.</p></div>\",\"PeriodicalId\":21057,\"journal\":{\"name\":\"Respiratory medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-06-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Respiratory medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0954611124001938\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0954611124001938","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Clofazimine serum concentration and safety/efficacy in nontuberculous mycobacterial pulmonary disease treatment
Background
Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD.
Methods
This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included.
Results
The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9–25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3–38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study.
Conclusion
CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.
期刊介绍:
Respiratory Medicine is an internationally-renowned journal devoted to the rapid publication of clinically-relevant respiratory medicine research. It combines cutting-edge original research with state-of-the-art reviews dealing with all aspects of respiratory diseases and therapeutic interventions. Topics include adult and paediatric medicine, epidemiology, immunology and cell biology, physiology, occupational disorders, and the role of allergens and pollutants.
Respiratory Medicine is increasingly the journal of choice for publication of phased trial work, commenting on effectiveness, dosage and methods of action.