Evidence map›Paper›PMID 28653479›Full record

ArticleClinical pharmacology and therapeutics2018

A Population Pharmacokinetic Model Incorporating Saturable Pharmacokinetics and Autoinduction for High Rifampicin Doses.

Robin J Svensson, Rob E Aarnoutse, Andreas H Diacon, Rodney Dawson, Stephen H Gillespie, Martin J Boeree, Ulrika S H Simonsson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical pharmacology and therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020
    Pooled it
  3. Pharmacokinetics of Dexamethasone in Tuberculous Meningitis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026
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  7. 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 · 2024
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Robin J SvenssonDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Rob E AarnoutseDepartment of Pharmacy, Radboud University Medical Center, Nijmegen, the Netherlands.
Andreas H DiaconDST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa and TASK Applied Sciences, Cape Town, South Africa.
Rodney DawsonDepartment of Respiratory Medicine, University of Cape Town, Cape Town, South Africa and The Lung Institute, Cape Town, South Africa.
Stephen H GillespieSchool of Medicine, University of St. Andrews, St. Andrews Fife, UK.
Martin J BoereeDepartment of Lung Diseases, Radboud University Medical Center, Nijmegen, the Netherlands and University Centre for Chronic Diseases Dekkerswald, Groesbeek, the Netherlands.
Ulrika S H SimonssonDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulating evidence suggests that increasing doses of rifampicin may shorten tuberculosis treatment. The PanACEA HIGHRIF1 trial assessed safety, pharmacokinetics, and antimycobacterial activity of rifampicin at doses up to 40 mg/kg. Eighty-three pulmonary tuberculosis patients received 10, 20, 25, 30, 35, or 40 mg/kg rifampicin daily over 2 weeks, supplemented with standard doses of isoniazid, pyrazinamide, and ethambutol in the second week. This study aimed at characterizing rifampicin pharmacokinetics observed in HIGHRIF1 using nonlinear mixed effects modeling. The final population pharmacokinetic model included an enzyme turnover model accounting for time-dependent elimination due to autoinduction, concentration-dependent clearance, and dose-dependent bioavailability. The relationship between clearance and concentration was characterized by a Michaelis-Menten relationship. The relationship between bioavailability and dose was described using an E

Indexed as

AdultAntibiotics, AntitubercularArea Under CurveBiological AvailabilityDose-Response Relationship, DrugDrug Dosage CalculationsDrug MonitoringDrug Therapy, CombinationFemaleHumansMaleModels, BiologicalRifampinTuberculosis, PulmonaryAntibiotics, AntitubercularRifampin

Identifiers

PMID28653479
PMCPMC5888114

What OpenQuestion holds

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Registered trials

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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.