ArticleThe Journal of antimicrobial chemotherapy2018
A model-informed preclinical approach for prediction of clinical pharmacodynamic interactions of anti-TB drug combinations.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Drug Effect of Clofazimine on Persisters Explains an Unexpected Increase in Bacterial Load in Patients.Antimicrobial agents and chemotherapy · 2020Trial
- Exposure to the four first-line anti-tuberculosis drugs and treatment outcomes: a target trial emulation study in Ghana.BMC infectious diseases · 2026Article
- Exposure to the Four First-Line Anti-Tuberculosis Drugs and Treatment Outcomes: A Target Trial Emulation Study in Ghana.Research square · 2026Article
- Pharmacokinetics-Pharmacodynamics Modeling for Evaluating Drug-Drug Interactions in Polypharmacy: Development and Challenges.Clinical pharmacokinetics · 2024Review
- The area under the effect curve as an efficacy determinant for anti-infectives.CPT: pharmacometrics & systems pharmacology · 2022Article
- Perspectives for systems biology in the management of tuberculosis.European respiratory review : an official journal of the European Respiratory Society · 2021Review
- Development of New Tuberculosis Drugs: Translation to Regimen Composition for Drug-Sensitive and Multidrug-Resistant Tuberculosis.Annual review of pharmacology and toxicology · 2021Review
- Anti-tuberculosis effect of isoniazid scales accurately from zebrafish to humans.British journal of pharmacology · 2020Article
- A model-based analysis identifies differences in phenotypic resistance between in vitro and in vivo: implications for translational medicine within tuberculosis.Journal of pharmacokinetics and pharmacodynamics · 2020Article
- Translational Assessment of Drug-Induced Proximal Tubule Injury Using a Kidney Microphysiological System.CPT: pharmacometrics & systems pharmacology · 2019Article
- Forecasting Clinical Dose-Response From Preclinical Studies in Tuberculosis Research: Translational Predictions With Rifampicin.Clinical pharmacology and therapeutics · 2018Article
- Comparisons of Analysis Methods for Assessment of Pharmacodynamic Interactions Including Design Recommendations.The AAPS journal · 2018Article
- A general pharmacodynamic interaction model identifies perpetrators and victims in drug interactions.Nature communications · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Identification of pharmacodynamic interactions is not reasonable to carry out in a clinical setting for many reasons. The aim of this work was to develop a model-informed preclinical approach for prediction of clinical pharmacodynamic drug interactions in order to inform early anti-TB drug development. Methods: In vitro time-kill experiments were performed with Mycobacterium tuberculosis using rifampicin, isoniazid or ethambutol alone as well as in different combinations at clinically relevant concentrations. The multistate TB pharmacometric (MTP) model was used to characterize the natural growth and exposure-response relationships of each drug after mono exposure. Pharmacodynamic interactions during combination exposure were characterized by linking the MTP model to the general pharmacodynamic interaction (GPDI) model with successful separation of the potential effect on each drug's potency (EC50) by the combining drug(s). Results: All combinations showed pharmacodynamic interactions at cfu level, where all combinations, except isoniazid plus ethambutol, showed more effect (synergy) than any of the drugs alone. Using preclinical information, the MTP-GPDI modelling approach was shown to correctly predict clinically observed pharmacodynamic interactions, as deviations from expected additivity. Conclusions: With the ability to predict clinical pharmacodynamic interactions, using preclinical information, the MTP-GPDI model approach outlined in this study constitutes groundwork for model-informed input to the development of new and enhancement of existing anti-TB combination regimens.
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