印度尼西亚结核性脑膜炎患者的异烟肼暴露和乙酰化酶状态

IF 2.8 3区医学 Q3 IMMUNOLOGY

Tuberculosis Pub Date : 2023-12-21 DOI:10.1016/j.tube.2023.102465

Vycke Yunivita , Lindsey te Brake , Sofiati Dian , Ahmad Rizal Ganiem , Reinout van Crevel , Rovina Ruslami , Rob Aarnoutse

{"title":"印度尼西亚结核性脑膜炎患者的异烟肼暴露和乙酰化酶状态","authors":"Vycke Yunivita , Lindsey te Brake , Sofiati Dian , Ahmad Rizal Ganiem , Reinout van Crevel , Rovina Ruslami , Rob Aarnoutse","doi":"10.1016/j.tube.2023.102465","DOIUrl":null,"url":null,"abstract":"<div>The effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life <130 min) or slow (half-life >130 min) acetylators. Slow acetylators had higher AUC0-24, Cmax and CSF concentrations than fast acetylators (GM AUC0-24 25.5 vs 10.6 mg/L*h, p < 0.001); plasma Cmax 5.5 vs 3.6 mg/L, p = 0.023; CSF concentration 1.9 vs 1.1 mg/L, p = 0.008). Higher isoniazid doses may benefit fast acetylators in TBM.</div>","PeriodicalId":23383,"journal":{"name":"Tuberculosis","volume":"144 ","pages":"Article 102465"},"PeriodicalIF":2.8000,"publicationDate":"2023-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Isoniazid exposures and acetylator status in Indonesian tuberculous meningitis patients\",\"authors\":\"Vycke Yunivita , Lindsey te Brake , Sofiati Dian , Ahmad Rizal Ganiem , Reinout van Crevel , Rovina Ruslami , Rob Aarnoutse\",\"doi\":\"10.1016/j.tube.2023.102465\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>The effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life <130 min) or slow (half-life >130 min) acetylators. Slow acetylators had higher AUC0-24, Cmax and CSF concentrations than fast acetylators (GM AUC0-24 25.5 vs 10.6 mg/L*h, p < 0.001); plasma Cmax 5.5 vs 3.6 mg/L, p = 0.023; CSF concentration 1.9 vs 1.1 mg/L, p = 0.008). Higher isoniazid doses may benefit fast acetylators in TBM.</div>\",\"PeriodicalId\":23383,\"journal\":{\"name\":\"Tuberculosis\",\"volume\":\"144 \",\"pages\":\"Article 102465\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-12-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tuberculosis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1472979223001889\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tuberculosis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1472979223001889","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

乙酰化酶状态对结核性脑膜炎（TBM）患者血浆和脑脊液中异烟肼暴露量的影响在很大程度上仍未得到探讨。在此，我们描述了 ReDEFINe 研究（NCT02169882）中 48 名受试者的异烟肼暴露量和乙酰化酶状态。50%的受试者是快速（半衰期为 130 分钟）或慢速（半衰期为 130 分钟）乙酰化者。与快速乙酰化者相比，慢乙酰化者的 AUC0-24、Cmax 和 CSF 浓度更高（GM AUC0-24 25.5 vs 10.6 mg/L*h，p < 0.001）；血浆 Cmax 5.5 vs 3.6 mg/L，p = 0.023；CSF 浓度 1.9 vs 1.1 mg/L，p = 0.008）。较高的异烟肼剂量可能有利于TBM中的快速乙酰化者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Isoniazid exposures and acetylator status in Indonesian tuberculous meningitis patients

The effect of acetylator status on the exposure to isoniazid in plasma and CSF in tuberculous meningitis (TBM) patients remains largely unexplored. Here, we describe isoniazid exposures and acetylator status of 48 subjects in the ReDEFINe study (NCT02169882). Fifty percentwere fast (half-life <130 min) or slow (half-life >130 min) acetylators. Slow acetylators had higher AUC_0-24, C_max and CSF concentrations than fast acetylators (GM AUC_0-24 25.5 vs 10.6 mg/L*h, p < 0.001); plasma C_max 5.5 vs 3.6 mg/L, p = 0.023; CSF concentration 1.9 vs 1.1 mg/L, p = 0.008). Higher isoniazid doses may benefit fast acetylators in TBM.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Tuberculosis 医学-呼吸系统

CiteScore

4.60

自引率

3.10%

发文量

审稿时长

49 days

期刊介绍： Tuberculosis is a speciality journal focusing on basic experimental research on tuberculosis, notably on bacteriological, immunological and pathogenesis aspects of the disease. The journal publishes original research and reviews on the host response and immunology of tuberculosis and the molecular biology, genetics and physiology of the organism, however discourages submissions with a meta-analytical focus (for example, articles based on searches of published articles in public electronic databases, especially where there is lack of evidence of the personal involvement of authors in the generation of such material). We do not publish Clinical Case-Studies. Areas on which submissions are welcomed include: -Clinical TrialsDiagnostics- Antimicrobial resistance- Immunology- Leprosy- Microbiology, including microbial physiology- Molecular epidemiology- Non-tuberculous Mycobacteria- Pathogenesis- Pathology- Vaccine development. This Journal does not accept case-reports. The resurgence of interest in tuberculosis has accelerated the pace of relevant research and Tuberculosis has grown with it, as the only journal dedicated to experimental biomedical research in tuberculosis.