Evidence map›Paper›PMID 29701775›Full record

SynthesisThe Journal of antimicrobial chemotherapy2018

Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis.

K E Stott, H Pertinez, M G G Sturkenboom, M J Boeree, R Aarnoutse, G Ramachandran, A Requena-Méndez, C Peloquin, C F N Koegelenberg, J W C Alffenaar and 5 more

Abstract readMeta-AnalysisSystematic Review
In one paragraph

Synthesis 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 62 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 5 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

62 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Effectiveness and Pharmacokinetic Exposures of First-Line Drugs Used to Treat Drug-Susceptible Tuberculosis in Children: A Systematic Review and Meta-Analysis.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023
    Pooled it
  4. Pooled it
  5. 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 · 2020
    Pooled it
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  9. 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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2 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

15 authors.

K E StottDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
H PertinezDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
M G G SturkenboomDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M J BoereeRadboud University Medical Center, Nijmegen, The Netherlands.
R AarnoutseRadboud University Medical Center, Nijmegen, The Netherlands.
G RamachandranDepartment of Biochemistry and Clinical Pharmacology, National Institute for Research in Tuberculosis, Chennai, India.
A Requena-MéndezCRESIB, Barcelona Institute for Global Health, University of Barcelona, Barcelona, Spain.
C PeloquinCollege of Pharmacy and Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
C F N KoegelenbergDepartment of Pulmonology, Stellenbosch University & Tygerberg Academic Hospital, Cape Town, South Africa.
J W C AlffenaarDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
R RuslamiDepartment of Pharmacology and Therapy, Universitas Padjadjaran, Bandung, Indonesia.
A TostmannDepartment of Primary and Community Care, Radboud University Medical Centre, Nijmegen, The Netherlands.
S SwaminathanIndian Council of Medical Research, New Delhi, India.
H McIlleronDivision of Clinical Pharmacology, University of Cape Town, Cape Town, South Africa.
G DaviesDepartment of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

Funding

Wellcome Trust 203919/Z/16/ZWellcome Trust 206379/Z/17/Z
6 · The paper itself

Abstract

Objectives: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. Methods: A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the Cmax and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I2 statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. Results: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with Cmax 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mg·h/L (SEM 2.60) and 38.73 mg·h/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. Conclusions: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field.

Indexed as

Healthy VolunteersAdministration, OralAdultAntibiotics, AntitubercularFemaleHumansMaleRifampinTuberculosisAntibiotics, AntitubercularRifampin

Identifiers

PMID29701775
PMCPMC6105874

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.