Evidence map›Paper›PMID 40020260›Full record

ArticleEBioMedicine2025

Development of an oral regimen of unithiol for the treatment of snakebite envenoming: a phase 1 open-label dose-escalation safety trial and pharmacokinetic analysis in healthy Kenyan adults.

Michael Abouyannis, Yvonne K Nyambura, Samson Ngome, Debra Riako, Jennifer Musyoki, Charles Muiruri, Benedict Orindi, Laura Else, Alieu Amara, Laura Dickinson and 11 more

Abstract readClinical Trial, Phase I
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

21 authors.

Michael AbouyannisCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool, UK; KEMRI-Wellcome Research Programme, Kilifi, Kenya. Electronic address: Michael.Abouyannis@lstmed.ac.uk.
Yvonne K NyamburaKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Samson NgomeKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Debra RiakoKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Jennifer MusyokiKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Charles MuiruriKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Benedict OrindiKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Laura ElseDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Alieu AmaraDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Laura DickinsonDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Rachel H ClareCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Laura-Oana AlbulescuCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Adam P WesthorpeCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Jeroen KoolDivision of BioAnalytical Chemistry, Amsterdam Institute of Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, the Netherlands; Centre for Analytical Sciences Amsterdam (CASA), 1098 XH, Amsterdam, the Netherlands.
Ifedayo AdetifaKEMRI-Wellcome Research Programme, Kilifi, Kenya; Department of Infectious Diseases Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.
Francis M NdunguKEMRI-Wellcome Research Programme, Kilifi, Kenya.
Richard FitzGeraldNIHR Royal Liverpool and Broadgreen CRF, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
Saye KhooDepartment of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK; NIHR Royal Liverpool and Broadgreen CRF, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK.
David G LallooCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Nicholas R CasewellCentre for Snakebite Research & Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Mainga HamalubaKEMRI-Wellcome Research Programme, Kilifi, Kenya; Centre for Tropical Medicine & Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundViperidae snakes are responsible for many of the 94,000 deaths caused by snakebite envenoming each year. The most pathological venom component of this globally diverse family of snakes are the zinc-dependent snake venom metalloproteinase (SVMP) enzymes, which can be inhibited by the metal chelator, unithiol. A short-course oral regimen, readily available and rapidly deployed ahead of hospital admission is needed.

methodsThis open-label, phase 1 clinical trial assessed the safety of single ascending oral, multiple ascending oral, and single ascending intravenous doses of unithiol in 64 healthy adult volunteers from Kilifi County, Kenya. The multiple dose stage was informed by an interim safety and pharmacokinetic analysis, and predefined target plasma concentrations. Plasma concentrations of unithiol were measured using high-performance liquid chromatography-mass spectrometry, and safety was described by full adverse event reporting.

findings175 individuals were screened, and 64 (median age 30 years, IQR 25-38 years) received the study drug. There were no dose limiting toxicities or serious adverse events. There were 61 solicited adverse events, 17 related unsolicited adverse events, and 53 laboratory adverse events, all of mild or moderate severity. The maximum oral dose of 1500 mg was well tolerated and associated with the following pharmacokinetic parameters: C

interpretationThe phase 2 recommended dose (1500 mg loading dose, followed by 900 mg doses at 6-h and 24-h) has no safety concerns, and has promising pharmacokinetic properties for clinical use. Unithiol is affordable, stable at room temperature, and has the potential to be given orally in remote rural clinics. Its further development for snakebite indication is warranted.

fundingWellcome Trust, Bloomsbury Set, and Cures Within Reach.

Indexed as

Snake BitesAdministration, OralAdultFemaleHealthy VolunteersHumansKenyaMaleEnvenomingPhase 1 clinical trialSnakebiteUnithiol

Identifiers

PMID40020260
PMCPMC11919382

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LicenceCC BY
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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.