Evidence map›Paper›PMID 36559163›Full record

ArticlePharmaceutics2022

Determination of the Pharmacokinetics and Pharmacodynamics of Isoniazid, Rifampicin, Pyrazinamide and Ethambutol in a Cross-Over Cynomolgus Macaque Model of

Laura Sibley, Andrew D White, Charlotte Sarfas, Jennie Gullick, Fergus Gleeson, Faye Lanni, Simon Clark, Emma Rayner, Santiago Ferrer-Bazaga, Fatima Ortega-Muro and 12 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 83% of its field
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

0 citing papers in PubMed, 1 citations in OpenAlex.

No citing paper in PubMed yet.

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

22 authors at 5 institutions in 2 countries.

Laura SibleyUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Andrew D WhiteUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.ORCID 0000-0001-9481-0079
Charlotte SarfasUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Jennie GullickUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Fergus GleesonDepartment of Oncology, Medical Sciences Division, Churchill Hospital, Oxford OX3 7DQ, UK.
Faye LanniUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Simon ClarkUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Emma RaynerUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Santiago Ferrer-BazagaDepartmento de Bioingenieria, Universidad Carlos III de Madrid, 28903 Madrid, Spain.ORCID 0000-0002-6672-551X
Fatima Ortega-MuroGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.
Laura AlamedaGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.
Joaquin RullasGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.
Veronica SousaGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.
Marisa MartinezGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.
Inigo Angulo-BarturenGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.ORCID 0000-0002-8800-8132
Adolfo GarciaGlaxoSmithKlein, Research and Development, Diseases of the Developing World, Severo Ochoa, 2., 28760 Madrid, Spain.
Juan José VaqueroDepartmento de Bioingenieria, Universidad Carlos III de Madrid, 28903 Madrid, Spain.ORCID 0000-0001-9200-361X
Henry E PertinezDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool L69 3GX, UK.
Geraint DaviesDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool L69 3GX, UK.
Mike DennisUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Ann WilliamsUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
Sally SharpeUK Health Security Agency, Research and Evaluation, Porton Down, Salisbury SP4 0JG, UK.
UK Health Security Agency · GBGlaxoSmithKline (Spain) · ESUniversidad Carlos III de Madrid · ESUniversity of Liverpool · GBChurchill Hospital · GB

Funding

EU Commission IMI Joint Undertaking 11537
6 · The paper itself

Abstract

Innovative cross-over study designs were explored in non-human primate (NHP) studies to determine the value of this approach for the evaluation of drug efficacy against tuberculosis (TB). Firstly, the pharmacokinetics (PK) of each of the drugs Isoniazid (H), Rifampicin (R), Pyrazinamide (Z) and Ethambutol (E), that are standardly used for the treatment of tuberculosis, was established in the blood of macaques after oral dosing as a monotherapy or in combination. Two studies were conducted to evaluate the pharmacokinetics and pharmacodynamics of different drug combinations using cross-over designs. The first employed a balanced, three-period Pigeon design with an extra period; this ensured that treatment by period interactions and carry-over could be detected comparing the treatments HR, HZ and HRZ using H37Rv as the challenge strain of

Indexed as

antibioticspharmacodynamicspharmacokineticsprimatestuberculosis

Identifiers

PMID36559163
PMCPMC9780811
OpenAlexW4311014309

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.