Sex-dependent variability of isoniazid and rifampicin serum levels in patients with tuberculosis.

IF 5.4 2区医学 Q1 INFECTIOUS DISEASES Infection Pub Date : 2024-11-12 DOI:10.1007/s15010-024-02424-5

Raja Idris, Alexander Z Dayani, Ana M Groh, André Mohr, Julia Koepsell, Ann-Sophie Zielbauer, Eva Herrmann, Maria J G T Vehreschild, Thomas A Wichelhaus, Nils Wetzstein

{"title":"Sex-dependent variability of isoniazid and rifampicin serum levels in patients with tuberculosis.","authors":"Raja Idris, Alexander Z Dayani, Ana M Groh, André Mohr, Julia Koepsell, Ann-Sophie Zielbauer, Eva Herrmann, Maria J G T Vehreschild, Thomas A Wichelhaus, Nils Wetzstein","doi":"10.1007/s15010-024-02424-5","DOIUrl":null,"url":null,"abstract":"Introduction: Drug-sensitive TB (DS-TB) is treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Factors like fast-metabolizing enzymes, malabsorption, and drug interactions can influence serum drug levels. Current TB treatment guidelines recommend weight-adapted dosing without considering sex differences. This study examines drug levels of isoniazid and rifampicin in TB patients treated between 2019 and 2023 at our center focusing on sex-specific aspects.Methods: Patients diagnosed with TB and available serum levels of isoniazid or rifampicin between 2019 and 2023 were retrospectively identified. Serum levels were measured using liquid chromatography-mass spectrometry and high-performance liquid chromatography. Patients were stratified by sex and a linear regression mixed effect model was used to assess predictors for different serum levels.Results: The study included 281 single therapeutic drug monitoring (TDM) measurements from 59 patients (28 women, 47.5%). For isoniazid, no sex-specific differences in serum drug levels were identified. On the other hand, female sex was a significant predictor of higher rifampicin plasma levels (coefficient 4.16, 95% CI 0.74-7.59, p = 0.009). Only 38.2% of rifampicin serum level measurements in male patients were within target range, the majority (40/68, 58.8%) were below range and only 2 (2.9%) TDM-levels were above range. Women displayed higher overall rifampicin serum levels than men (median 13.7 mg/l vs. 7.1 mg/l, p = 0.04), although weight adjusted doses were not significantly different (median 10.0 mg/kg vs. 9.8 mg/kg p = 0.56). Adverse effects were noted in 42.9% (42/98) of measurements in women and 29.5% (54/183) of measurements in men (p = 0.03).Discussion: Rifampicin levels were significantly lower in men compared to women, despite weight-adjusted dosing. Clinicians should consider TDM and potential sex differences when treating patients with TB.","PeriodicalId":13600,"journal":{"name":"Infection","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infection","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s15010-024-02424-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Drug-sensitive TB (DS-TB) is treated with isoniazid, rifampicin, ethambutol, and pyrazinamide. Factors like fast-metabolizing enzymes, malabsorption, and drug interactions can influence serum drug levels. Current TB treatment guidelines recommend weight-adapted dosing without considering sex differences. This study examines drug levels of isoniazid and rifampicin in TB patients treated between 2019 and 2023 at our center focusing on sex-specific aspects.

Methods: Patients diagnosed with TB and available serum levels of isoniazid or rifampicin between 2019 and 2023 were retrospectively identified. Serum levels were measured using liquid chromatography-mass spectrometry and high-performance liquid chromatography. Patients were stratified by sex and a linear regression mixed effect model was used to assess predictors for different serum levels.

Results: The study included 281 single therapeutic drug monitoring (TDM) measurements from 59 patients (28 women, 47.5%). For isoniazid, no sex-specific differences in serum drug levels were identified. On the other hand, female sex was a significant predictor of higher rifampicin plasma levels (coefficient 4.16, 95% CI 0.74-7.59, p = 0.009). Only 38.2% of rifampicin serum level measurements in male patients were within target range, the majority (40/68, 58.8%) were below range and only 2 (2.9%) TDM-levels were above range. Women displayed higher overall rifampicin serum levels than men (median 13.7 mg/l vs. 7.1 mg/l, p = 0.04), although weight adjusted doses were not significantly different (median 10.0 mg/kg vs. 9.8 mg/kg p = 0.56). Adverse effects were noted in 42.9% (42/98) of measurements in women and 29.5% (54/183) of measurements in men (p = 0.03).

Discussion: Rifampicin levels were significantly lower in men compared to women, despite weight-adjusted dosing. Clinicians should consider TDM and potential sex differences when treating patients with TB.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

结核病患者异烟肼和利福平血清水平的性别差异。

导言：药物敏感型肺结核（DS-TB）采用异烟肼、利福平、乙胺丁醇和吡嗪酰胺进行治疗。快速代谢酶、吸收不良和药物相互作用等因素会影响血清药物浓度。目前的结核病治疗指南建议采用与体重相适应的剂量，但未考虑性别差异。本研究对本中心 2019 年至 2023 年接受治疗的肺结核患者的异烟肼和利福平药物水平进行了研究，重点关注性别特异性：方法：回顾性地确定了 2019 年至 2023 年期间被诊断为肺结核的患者，并获得了异烟肼或利福平的血清水平。使用液相色谱-质谱法和高效液相色谱法测量血清水平。根据性别对患者进行分层，并使用线性回归混合效应模型评估不同血清水平的预测因素：研究包括来自 59 名患者（28 名女性，占 47.5%）的 281 次治疗药物监测（TDM）测量结果。在异烟肼方面，没有发现血清药物水平的性别差异。另一方面，女性是预测利福平血浆水平较高的重要因素（系数 4.16，95% CI 0.74-7.59，p = 0.009）。男性患者中只有 38.2% 的利福平血清水平测量值在目标范围内，大多数（40/68，58.8%）低于目标范围，只有 2 例（2.9%）TDM 水平高于目标范围。女性的利福平血清总水平高于男性（中位数为 13.7 毫克/升 vs. 7.1 毫克/升，p = 0.04），尽管体重调整剂量没有显著差异（中位数为 10.0 毫克/千克 vs. 9.8 毫克/千克，p = 0.56）。42.9%（42/98）的女性测量结果和29.5%（54/183）的男性测量结果出现了不良反应（p = 0.03）：讨论：尽管采用了体重调整剂量，但男性的利福平水平明显低于女性。临床医生在治疗肺结核患者时应考虑TDM和潜在的性别差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.