ArticleClinical pharmacokinetics2023
Predictions of Bedaquiline and Pretomanid Target Attainment in Lung Lesions of Tuberculosis Patients using Translational Minimal Physiologically Based Pharmacokinetic Modeling.
Article in Clinical pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.The Journal of infectious diseases · 2025Article
- Bedaquiline Delivery Innovations: A Review on Advancing MDR-TB Treatment Strategies.Recent advances in anti-infective drug discovery · 2025Review
- Relative Contributions of the Novel Diarylquinoline TBAJ-876 and its Active Metabolite to the Bactericidal Activity in a Murine Model of Tuberculosis.The Journal of infectious diseases · 2024Article
- Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs.Nature communications · 2024Observational
- Predictions of Bedaquiline Central Nervous System Exposure in Patients with Tuberculosis Meningitis Using Physiologically based Pharmacokinetic Modeling.Clinical pharmacokinetics · 2024Article
- Dynamic PET Reveals Compartmentalized Brain and Lung Tissue Antibiotic Exposures.Research square · 2024Article
- stormTB: a web-based simulator of a murine minimal-PBPK model for anti-tuberculosis treatments.Frontiers in pharmacology · 2024Article
- A minimal PBPK model to accelerate preclinical development of drugs against tuberculosis.Frontiers in pharmacology · 2023Article
- Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline againstFrontiers in medicine · 2023Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSite-of-action concentrations for bedaquiline and pretomanid from tuberculosis patients are unavailable. The objective of this work was to predict bedaquiline and pretomanid site-of-action exposures using a translational minimal physiologically based pharmacokinetic (mPBPK) approach to understand the probability of target attainment (PTA).
methodsA general translational mPBPK framework for the prediction of lung and lung lesion exposure was developed and validated using pyrazinamide site-of-action data from mice and humans. We then implemented the framework for bedaquiline and pretomanid. Simulations were conducted to predict site-of-action exposures following standard bedaquiline and pretomanid, and bedaquiline once-daily dosing. Probabilities of average concentrations within lesions and lungs greater than the minimum bactericidal concentration for non-replicating (MBC
resultsThe translational modeling approach was successful in predicting pyrazinamide lung concentrations from mice to patients. We predicted that 94% and 53% of patients would attain bedaquiline average daily PK exposure within lesions (C
conclusionsThe translational mPBPK model predicted that the standard bedaquiline continuation phase and standard pretomanid dosing may not achieve optimal exposures to eradicate non-replicating bacteria in most patients.
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