Trial reportAntimicrobial agents and chemotherapy2012
A semimechanistic pharmacokinetic-enzyme turnover model for rifampin autoinduction in adult tuberculosis patients.
Trial report in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 2 of them syntheses that pooled it.
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
60 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Rifapentine Population Pharmacokinetics and Dosing Recommendations for Latent Tuberculosis Infection.American journal of respiratory and critical care medicine · 2020Pooled it
- A systematic review and meta-analysis of first-line tuberculosis drug concentrations and treatment outcomes.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2020Pooled it
- Pharmacokinetic-Pharmacodynamic Evidence From a Phase 3 Trial to Support Flat-Dosing of Rifampicin for Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Trial
- Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis.Clinical pharmacology and therapeutics · 2020Trial
- Rifampin Pharmacokinetics and Safety in Preterm and Term Infants.Antimicrobial agents and chemotherapy · 2019Trial
- Optimization of dosing regimens of isoniazid and rifampicin in children with tuberculosis in India.British journal of clinical pharmacology · 2019Trial
- Artificial intelligence-derived 3-Way Concentration-dependent Antagonism of Gatifloxacin, Pyrazinamide, and Rifampicin During Treatment of Pulmonary Tuberculosis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2018Trial
- Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2017Trial
- A pharmacometric pulmonary model predicting the extent and rate of distribution from plasma to epithelial lining fluid and alveolar cells--using rifampicin as an example.European journal of clinical pharmacology · 2015Trial
- Towards Model-Informed Precision Dosing of High-Dose Rifampicin: A Parsimonious Population Pharmacokinetic Model Capturing Saturation and Autoinduction in Tanzanian and South African Patients with Tuberculosis.Clinical pharmacokinetics · 2026Article
- Rifampicin as an antivirulence adjunct in hypervirulent/hypermucoviscous Klebsiella pneumoniae infections: a scoping review.BMC infectious diseases · 2026Article
- Population Pharmacokinetic Modeling of Encorafenib in Healthy Participants and Patients with BRAF V600-Mutant Solid Tumors: A Semi-mechanistic Autoinduction Model.Clinical pharmacokinetics · 2026Article
- Exposure to Rifampicin and its Metabolite 25-Deacetylrifampicin Rapidly Decreases During Tuberculosis Therapy.Clinical pharmacokinetics · 2025Article
- Pharmacometrics modeling and simulation to assist phenobarbital dose optimization in dogs.Frontiers in veterinary science · 2025Article
- Parametric Population Pharmacokinetics Model Repository of Rifampicin: Model-Informed Individualized Therapy.Clinical pharmacology : advances and applications · 2025Article
- State of the art of real-life concentration monitoring of rifampicin and its implementation contextualized in resource-limited settings: the Tanzanian case.JAC-antimicrobial resistance · 2024Review
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Pharmacokinetics of anti-Mycobacterium avium-intracellulare disease drugs in silkworms.Scientific reports · 2024Article
- Article
- Inter-Species Pharmacokinetic Modeling and Scaling for Drug Repurposing of Pyronaridine and Artesunate.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 7 countries.
Funding
Abstract
The currently recommended doses of rifampin are believed to be at the lower end of the dose-response curve. Rifampin induces its own metabolism, although the effect of dose on the extent of autoinduction is not known. This study aimed to investigate rifampin autoinduction using a semimechanistic pharmacokinetic-enzyme turnover model. Four different structural basic models were explored to assess whether different scaling methods affected the final covariate selection procedure. Covariates were selected by using a linearized approach. The final model included the allometric scaling of oral clearance and apparent volume of distribution. Although HIV infection was associated with a 30% increase in the apparent volume of distribution, simulations demonstrated that the effect of HIV on rifampin exposure was slight. Model-based simulations showed close-to-maximum induction achieved after 450-mg daily dosing, since negligible increases in oral clearance were observed following the 600-mg/day regimen. Thus, dosing above 600 mg/day is unlikely to result in higher magnitudes of autoinduction. In a typical 55-kg male without HIV infection, the oral clearance, which was 7.76 liters · h⁻¹ at the first dose, increased 1.82- and 1.85-fold at steady state after daily dosing with 450 and 600 mg, respectively. Corresponding reductions of 41 and 42%, respectively, in the area under the concentration-versus-time curve from 0 to 24 h were estimated. The turnover of the inducible process was estimated to have a half-life of approximately 8 days in a typical patient. Assuming 5 half-lives to steady state, this corresponds to a duration of approximately 40 days to reach the induced state for rifampin autoinduction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.