ArticleThe Journal of antimicrobial chemotherapy2024
The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs.
Article in The Journal of antimicrobial chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Pharmacokinetics of ethambutol and weight banded dosing in South African adults newly diagnosed with tuberculosis and HIV.Antimicrobial agents and chemotherapy · 2025Trial
- Insights into the Role of Rifampicin Exposure and Clinical Baseline Covariates on the Response to Pulmonary Tuberculosis Treatment.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Convolutional neural networks quantify antibiotic resistance in Mycobacterium tuberculosis with diagnostic grade accuracy and predict treatment response.Nature communications · 2026Article
- A Pragmatic Approach to Handling Censored Data Below the Lower Limit of Quantification in Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2025Article
- The effect of pregnancy on the population pharmacokinetics of levofloxacin in South Africans with rifampicin-resistant tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
backgroundIn South Africa, an estimated 11% of the population have high alcohol use, a major risk factor for TB. Alcohol and other substance use are also associated with poor treatment response, with a potential mechanism being altered TB drug pharmacokinetics.
objectivesTo investigate the impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs in participants with pulmonary TB.
methodsWe prospectively enrolled participants ≥15 years old, without HIV, and initiating drug-susceptible TB treatment in Worcester, South Africa. Alcohol use was measured via self-report and blood biomarkers. Other illicit substances were captured through a urine drug test. Plasma samples were drawn 1 month into treatment pre-dose, and 1.5, 3, 5 and 8 h post-dose. Non-linear mixed-effects modelling was used to describe the pharmacokinetics of rifampicin, isoniazid, pyrazinamide and ethambutol. Alcohol and drug use were tested as covariates.
resultsThe study included 104 participants, of whom 70% were male, with a median age of 37 years (IQR 27-48). Alcohol use was high, with 42% and 28% of participants having moderate and high alcohol use, respectively. Rifampicin and isoniazid had slightly lower pharmacokinetics compared with previous reports, whereas pyrazinamide and ethambutol were consistent. No significant alcohol use effect was detected, other than 13% higher ethambutol clearance in participants with high alcohol use. Methaqualone use reduced rifampicin bioavailability by 19%.
conclusionNo clinically relevant effect of alcohol use was observed on the pharmacokinetics of first-line TB drugs, suggesting that poor treatment outcome is unlikely due to pharmacokinetic alterations. That methaqualone reduced rifampicin means dose adjustment may be beneficial.
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