Trial reportThe Journal of antimicrobial chemotherapy2019
Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.
Trial report in The Journal of antimicrobial chemotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- Pharmacokinetics of ethambutol and weight banded dosing in South African adults newly diagnosed with tuberculosis and HIV.Antimicrobial agents and chemotherapy · 2025Trial
- High Isoniazid Exposures When Administered with Rifapentine Once Weekly for Latent Tuberculosis in Individuals with Human Immunodeficiency Virus.Antimicrobial agents and chemotherapy · 2023Trial
- Pharmacokinetics and Drug-Drug Interactions of Isoniazid and Efavirenz in Pregnant Women Living With HIV in High TB Incidence Settings: Importance of Genotyping.Clinical pharmacology and therapeutics · 2021Trial
- CYP2B6 Genotype-Dependent Inhibition of CYP1A2 and Induction of CYP2A6 by the Antiretroviral Drug Efavirenz in Healthy Volunteers.Clinical and translational science · 2019Trial
- Pharmacokinetics of first-line tuberculosis drugs rifampin, isoniazid, ethambutol, and pyrazinamide during pregnancy and postpartum with and without efavirenz-based antiretroviral treatment: IMPAACT P1026s study.Antimicrobial agents and chemotherapy · 2025Article
- Precision Medicine Strategies to Improve Isoniazid Therapy in Patients with Tuberculosis.European journal of drug metabolism and pharmacokinetics · 2024Review
- Pharmacokinetics and pharmacodynamics of high-dose isoniazid for the treatment of rifampicin- or multidrug-resistant tuberculosis in Indonesia.The Journal of antimicrobial chemotherapy · 2024Observational
- Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy.Clinical and translational science · 2023Article
- Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.PLoS medicine · 2023Article
- The immunogenetics of tuberculosis (TB) susceptibility.Immunogenetics · 2023Review
- Optimizing Moxifloxacin Dose in MDR-TB Participants with or without Efavirenz Coadministration Using Population Pharmacokinetic Modeling.Antimicrobial agents and chemotherapy · 2023Article
- Influence of NAT2 Genotype and Maturation on Isoniazid Exposure in Low-Birth-Weight and Preterm Infants With or Without Human Immunodeficiency Virus (HIV) Exposure.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Article
- Pharmacokinetics of standard versus high-dose isoniazid for treatment of multidrug-resistant tuberculosis.The Journal of antimicrobial chemotherapy · 2022Observational
- Pharmacokinetic analysis of linezolid for multidrug resistant tuberculosis at a tertiary care centre in Mumbai, India.Frontiers in pharmacology · 2022Article
- Evaluation of the estimation and classification performance of NONMEM when applying mixture model for drug clearance.CPT: pharmacometrics & systems pharmacology · 2021Article
- Article
- A Model-Informed Method for the Purpose of Precision Dosing of Isoniazid in Pulmonary Tuberculosis.Clinical pharmacokinetics · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Mycobacterium tuberculosis precursor rRNA as a measure of treatment-shortening activity of drugs and regimens.Nature communications · 2021Article
- Acetylation of Isoniazid Is a Novel Mechanism of Isoniazid Resistance in Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 5 countries.
Funding
Abstract
Objectives: To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of isoniazid and acetyl-isoniazid. Methods: TB/HIV-coinfected patients participating in the three-treatment-arm RAFA randomized controlled trial conducted in West Africa were recruited into the pharmacokinetics sub-study. Five serial blood samples were collected on a single visit between 4 and 8 weeks after initiation of antituberculosis treatment. Concentration-time data for isoniazid and acetyl-isoniazid were analysed using non-linear mixed-effects models. Results: Isoniazid concentrations from 150 patients were available for analysis, and 79 of these (53%) also had concentrations of acetyl-isoniazid. Isoniazid pharmacokinetics was best described with a two-compartment disposition model with lagged first-order absorption and elimination using a semi-mechanistic model describing hepatic extraction. The model identified two elimination pathways, separating formation of acetyl-isoniazid from other routes of metabolism. The predicted AUC0-24 is reduced by 29% in patients who are fast acetylators of isoniazid and receiving efavirenz-based ART (6.73 versus 4.68 mg·h/L). In slow acetylators, efavirenz-based ART had no effect on isoniazid exposure (AUC0-24 = 17.5 mg·h/L). Conclusions: Efavirenz-based ART affects the acetylation metabolic pathway amongst rapid acetylators, resulting in reduced exposure to isoniazid. Pharmacokinetics of isoniazid and acetyl-isoniazid were not influenced by the 50% increase in rifampicin dose.
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Registered trials
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