Sex-dependent variability of isoniazid and rifampicin serum levels in patients with tuberculosis.
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 consideri...
| Publicado en: | Infection Vol. 53; no. 3; pp. 1051 - 1061 |
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| Autores principales: | , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jun2025
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=185686817&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 185686817 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 03008126 NXO jtl: Infection issn: 03008126 maglogo: N pubinfo: dt: Jun2025 vid: 53 iid: 3 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 185686817 180818428 185686817 185686817 10.1007/s15010-024-02424-5 185686817 ppf: 1051 ppct: 10 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Sex-dependent variability of isoniazid and rifampicin serum levels in patients with tuberculosis. aug: au: Idris, Raja Dayani, Alexander Z. Groh, Ana M. Mohr, André Koepsell, Julia Zielbauer, Ann-Sophie Herrmann, Eva Vehreschild, Maria J. G. T. Wichelhaus, Thomas A. Wetzstein, Nils affil: https://ror.org/04cvxnb49 Department of Internal Medicine, Infectious Diseases, University Hospital, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany sug: subj: Tuberculosis Blood Isoniazid Blood Rifampin Blood Antitubercular Agents Blood Tuberculosis Drug Therapy Isoniazid Therapeutic Use Rifampin Therapeutic Use Antitubercular Agents Therapeutic Use Sex Factors Drug Monitoring Human Male Female Adult Retrospective Design Record Review Liquid Chromatography-Mass Spectrometry Methods Chromatography, High Pressure Liquid Methods Linear Regression Models, Theoretical Predictive Value of Tests Isoniazid Adverse Effects Rifampin Adverse Effects Antitubercular Agents Adverse Effects Confidence Intervals Data Analysis Software Descriptive Statistics Adult: 19-44 years Male Female ab: 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. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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