Evidence map›Paper›PMID 35668346›Full record

ArticleClinical pharmacokinetics2022

Population Pharmacokinetics of Delamanid and its Main Metabolite DM-6705 in Drug-Resistant Tuberculosis Patients Receiving Delamanid Alone or Coadministered with Bedaquiline.

Lénaïg Tanneau, Mats O Karlsson, Andreas H Diacon, Justin Shenje, Jorge De Los Rios, Lubbe Wiesner, Caryn M Upton, Kelly E Dooley, Gary Maartens, Elin M Svensson

Open access · hybridAbstract read
In one paragraph

Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Effect of HIV on bedaquiline and delamanid pharmacokinetics in patients with multidrug-resistant TB.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2025
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  10. Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024
    Review
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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

10 authors at 5 institutions in 5 countries.

Lénaïg TanneauDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.
Mats O KarlssonDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.
Andreas H DiaconTASK Applied Science, Cape Town, South Africa.
Justin ShenjeSATVI, University of Cape Town, Cape Town, South Africa.
Jorge De Los RiosBarranco Clinical Research Site, Asociacion Civil Impacta Salud y Educacion, Lima, Peru.
Lubbe WiesnerDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Caryn M UptonTASK Applied Science, Cape Town, South Africa.
Kelly E DooleyCenter for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Gary MaartensDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Elin M SvenssonDepartment of Pharmacy, Uppsala University, Uppsala, Sweden. elin.svensson@farmaci.uu.se.ORCID 0000-0002-0093-6445
University of Cape Town · ZAUppsala University · SETask Applied Science · ZAAsociación Civil Impacta Salud y Educación · PEJohns Hopkins University · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
Validation, CLIA and Qualification (VQC): Enhancing the RS ratio as a tool for AIDS Clinical Trial Group (ACTG) tuberculosis trialsUM1AI106701 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Grace M Aldrovandi · 2014 to 2026
$116.8M
University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit 2024 SupplementUM1AI069423 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, MINA CHRISTINE HOSSEINIPOUR · 2012 to 2026
$71.8M
Mentoring Investigators in HIV and Tuberculosis Therapeutics ResearchK24AI150349 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DOOLEY, KELLY E. · 2020 to 2025
$789k
NIAID NIH HHS K24 AI150349NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069423NIAID NIH HHS UM1 AI106701
6 · The paper itself

Abstract

BACKGROUND AND

objectiveDelamanid is a nitroimidazole, a novel class of drug for treating tuberculosis, and is primarily metabolized by albumin into the metabolite DM-6705. The aims of this analysis were to develop a population pharmacokinetic (PK) model to characterize the concentration-time course of delamanid and DM-6705 in adults with drug-resistant tuberculosis and to explore a potential drug-drug interaction with bedaquiline when coadministered.

methodsDelamanid and DM-6705 concentrations after oral administration, from 52 participants (of whom 26 took bedaquiline concurrently and 20 were HIV-1 positive) enrolled in the DELIBERATE trial were analyzed using nonlinear mixed-effects modeling.

resultsDelamanid PK were described by a one-compartment disposition model with transit compartment absorption (mean absorption time of 1.45 h [95% confidence interval 0.501-2.20]) and linear elimination, while the PK of DM-6705 metabolite were described by a one-compartment disposition model with delamanid clearance as input and linear elimination. Predicted terminal half-life values for delamanid and DM-6705 were 15.1 h and 7.8 days, respectively. The impact of plasma albumin concentrations on delamanid metabolism was not significant. Bedaquiline coadministration did not affect delamanid PK. Other than allometric scaling with body weight, no patients' demographics were significant (including HIV).

conclusionsThis is the first joint PK model of delamanid and its DM-6705 metabolite. As such, it can be utilized in future exposure-response or exposure-safety analyses. Importantly, albumin concentrations, bedaquiline coadministration, and HIV co-infection (dolutegravir coadministration) did not have an effect on delamanid and DM-6705 PK.

Indexed as

HIV InfectionsNitroimidazolesTuberculosis, Multidrug-ResistantAdultAlbuminsAntitubercular AgentsDiarylquinolinesHumansOxazolesAlbuminsAntitubercular AgentsbedaquilineDiarylquinolinesNitroimidazolesOPC-67683Oxazoles

Identifiers

PMID35668346
PMCPMC9349160
OpenAlexW4281781162

What OpenQuestion holds

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LicenceCC BY-NC
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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.