Evidence map›Paper›PMID 37090528›Full record

ArticlebioRxiv : the preprint server for biology2023

Using dynamic oral dosing of rifapentine and rifabutin to simulate exposure profiles of long-acting formulations in a mouse model of tuberculosis preventive therapy.

Yong S Chang, Si-Yang Li, Henry Pertinez, Fabrice Betoudji, Jin Lee, Steven P Rannard, Andrew Owen, Eric L Nuermberger, Nicole C Ammerman

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. 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
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, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Yong S ChangCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Si-Yang LiCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Henry PertinezCentre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Fabrice BetoudjiCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jin LeeCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Steven P RannardCentre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Andrew OwenCentre of Excellence in Long-acting Therapeutics (CELT), Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.
Eric L NuermbergerCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nicole C AmmermanCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Johns Hopkins University · USUniversity of Liverpool · GB

Funding

Vaccine Response and Immunotherapeutics SWGP30AI094189 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Richard E. Chaisson · 2012 to 2026
$67.0M
Harnessing potent next-generation diarylquinolines for long-acting injectable formulations to prevent and treat tuberculosisR61AI161809 · NIAID · JOHNS HOPKINS UNIVERSITY · PI NUERMBERGER, ERIC L · 2021 to 2023
$1.7M
NIAID NIH HHS P30 AI094189NIAID NIH HHS R61 AI161809
6 · The paper itself

Abstract

Administration of tuberculosis preventive therapy (TPT) to individuals with latent tuberculosis infection is an important facet of global tuberculosis control. The use of long-acting injectable (LAI) drug formulations may simplify and shorten regimens for this indication. Rifapentine and rifabutin have anti-tuberculosis activity and physiochemical properties suitable for LAI formulation, but there are limited data available for determining the target exposure profiles required for efficacy in TPT regimens. The objective of this study was to determine exposure-activity profiles of rifapentine and rifabutin to inform development of LAI formulations for TPT. We utilized a validated paucibacillary mouse model of TPT in combination with dynamic oral dosing of both drugs to simulate and understand exposure-activity relationships to inform posology for future LAI formulations. This work identified several LAI-like exposure profiles of rifapentine and rifabutin that, if achieved by LAI formulations, could be efficacious as TPT regimens and thus can serve as experimentally-determined targets for novel LAI formulations of these drugs. We present novel methodology to understand the exposure-response relationship and inform the value proposition for investment in development of LAI formulations that has utility beyond latent tuberculosis infection.

Identifiers

PMID37090528
PMCPMC10120629
OpenAlexW4365455114

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.