ArticleBritish journal of clinical pharmacology2020
Understanding the drug exposure-response relationship of bedaquiline to predict efficacy for novel dosing regimens in the treatment of multidrug-resistant tuberculosis.
Article in British journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed.
- Bioequivalence Study of Bedaquiline and SirturoDrugs in R&D · 2025Trial
- Establishing the Exposure-QT Relationship During Bedaquiline Treatment Using a Time-Varying Tuberculosis-Specific Correction Factor (QTcTBT).CPT: pharmacometrics & systems pharmacology · 2025Trial
- A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.The Journal of antimicrobial chemotherapy · 2024Trial
- Exposure-safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Phase 2C clinical trial of novel short-course regimens for the treatment of pulmonary tuberculosis: TBTC study 38/CRUSH-TB design.Contemporary clinical trials · 2025Article
- Using Machine Learning Methods to Predict Early Treatment Outcomes for Multidrug-Resistant or Rifampicin-Resistant Tuberculosis to Enhance Patient Cure Rates: Development and Validation of Multiple Models.Journal of medical Internet research · 2025Article
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Bedaquiline Resistance after Effective Treatment of Multidrug-Resistant Tuberculosis, Namibia.Emerging infectious diseases · 2024Article
- Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline againstFrontiers in medicine · 2023Review
- Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients.Frontiers in pharmacology · 2023Article
- Pharmacogenetics of Between-Individual Variability in Plasma Clearance of Bedaquiline and Clofazimine in South Africa.The Journal of infectious diseases · 2022Article
- A modeling-based proposal for safe and efficacious reintroduction of bedaquiline after dose interruption: A population pharmacokinetics study.CPT: pharmacometrics & systems pharmacology · 2022Article
- A Scoping Review of the Clinical Pharmacokinetics of Bedaquiline.Clinical pharmacokinetics · 2022Article
- Pharmacodynamics and Bactericidal Activity of Bedaquiline in Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2022Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Understanding the drug exposure-response relationship of bedaquiline to predict efficacy for novel dosing regimens in the treatment of multidrug-resistant tuberculosis.British journal of clinical pharmacology · 2020Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
aimsTo externally validate an earlier characterized relationship between bedaquiline exposure and decline in bacterial load in a more difficult-to-treat patient population, and to explore the performances of alternative dosing regimens through simulations.
methodsThe bedaquiline exposure-response relationship was validated using time-to-positivity data from 233 newly diagnosed or treatment-experienced patients with drug-resistant tuberculosis from the C209 open-label study. The significance of the exposure-response relationship on the bacterial clearance was compared to a constant drug effect model. Tuberculosis resistance type and the presence and duration of antituberculosis pre-treatment were evaluated as additional covariates. Alternative dosing regimens were simulated for tuberculosis patients with different types of drug resistance.
resultsHigh bedaquiline concentrations were confirmed to be associated with faster bacterial load decline in patients, given that the exposure-effect relationship provided a significantly better fit than the constant drug effect (relative likelihood = 0.0003). The half-life of bacterial clearance was identified to be 22% longer in patients with pre-extensively drug-resistant (pre-XDR) tuberculosis (TB) and 86% longer in patients with extensively drug-resistant (XDR) TB, compared to patients with multidrug-resistant (MDR) TB. Achievement of the same treatment response for (pre-)XDR TB patients as for MDR TB patients would be possible by adjusting the dose and dosing frequency. Furthermore, daily bedaquiline administration as in the ZeNix regimen, was predicted to be as effective as the approved regimen.
conclusionThe confirmed bedaquiline exposure-response relationship offers the possibility to predict efficacy under alternative dosing regimens, and provides a useful tool for potential treatment optimization.
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