Development of An Optimised Oral Regimen of Unithiol for the Treatment of Snakebite Envenoming: a Phase 1 Dose-Escalation Trial and Pharmacokinetic Analysis in Healthy Kenyan Adults DOI
Michael Abouyannis,

Yvonne K. Nyambura,

Samson Ngome

et al.

Published: Jan. 1, 2024

Background: Viperidae snakes are responsible for many of the 94,000 deaths caused by snakebite envenoming each year. The most pathological venom component this globally diverse family zinc-dependent snake metalloproteinase (SVMP) enzymes, which can be inhibited metal chelator, unithiol. A short-course oral regimen, readily available and rapidly deployed ahead hospital admission is needed. Methods: This open-label, phase 1 clinical trial assessed safety single ascending oral, multiple intravenous doses unithiol in 64 healthy adult volunteers from Kilifi County, Kenya. dose stage was informed an interim pharmacokinetic analysis, predefined target plasma concentrations. Plasma concentrations were measured using high-performance liquid chromatography-mass spectrometry, described full adverse event reporting. Findings: 175 individuals screened, (median age 30 years, IQR 25-38 years) received study drug. There no limiting toxicities or serious events. 61 solicited events, 17 related unsolicited 53 laboratory all mild moderate severity. maximum 1,500 mg well tolerated demonstrated a Cmax that equivalent to administration. Interpretation: 2 recommended (1,500 loading dose, followed 900 at 6-hours 24-hours) safe, has promising properties use. Unithiol affordable, stable room temperature, potential given orally remote rural clinics. Its further development indication warranted. Trial Registration: registered on Pan African Clinical Trials Registry (PACTR202103718625048)Funding: Wellcome Trust, Bloomsbury Set, Cures Within Reach.Declaration Interest: competing interests study.Ethical Approval: obtained ethical approval Kenya Medical Research Institute Scientific Ethics Review Unit (192/4106) Liverpool School Tropical Medicine Committee (20-032), regulatory Pharmacy Poisons Board (136). conducted accordance with requirements, including International Conference Harmonisation-Good Practice guidelines.

Language: Английский

Qualitative Profiling of Venom Toxins in the Venoms of Several Bothrops Species Using High-Throughput Venomics and Coagulation Bioassaying DOI Creative Commons

Dimoetsha J. C. Weekers,

Luis L. Alonso,

Anniek X. Verstegen

et al.

Toxins, Journal Year: 2024, Volume and Issue: 16(7), P. 300 - 300

Published: July 1, 2024

Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization.

Language: Английский

Citations

2
Metabolomics‐driven approaches for identifying therapeutic targets in drug discovery DOI Creative Commons

Sophearith Pan,

Lichang Yin, Jie Liu

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Nov. 1, 2024

Abstract Identification of therapeutic targets can directly elucidate the mechanism and effect drug therapy, which is a central step in development. The disconnect between protein phenotypes under complex mechanisms hampers comprehensive target understanding. Metabolomics, as systems biology tool that captures phenotypic changes induced by exogenous compounds, has emerged valuable approach for identification. A overview was provided this review to illustrate principles advantages metabolomics, delving into application metabolomics This outlines various metabolomics‐based methods, such dose–response stable isotope‐resolved multiomics, identify key enzymes metabolic pathways affected substances through dose‐dependent metabolite–drug interactions. Emerging techniques, including single‐cell artificial intelligence, mass spectrometry imaging, are also explored their potential enhance discovery. emphasizes metabolomics' critical role advancing our understanding disease accelerating targeted development, while acknowledging current challenges field.

Language: Английский

Citations

2
Development of An Optimised Oral Regimen of Unithiol for the Treatment of Snakebite Envenoming: a Phase 1 Dose-Escalation Trial and Pharmacokinetic Analysis in Healthy Kenyan Adults DOI
Michael Abouyannis,

Yvonne K. Nyambura,

Samson Ngome

et al.

Published: Jan. 1, 2024

Background: Viperidae snakes are responsible for many of the 94,000 deaths caused by snakebite envenoming each year. The most pathological venom component this globally diverse family zinc-dependent snake metalloproteinase (SVMP) enzymes, which can be inhibited metal chelator, unithiol. A short-course oral regimen, readily available and rapidly deployed ahead hospital admission is needed. Methods: This open-label, phase 1 clinical trial assessed safety single ascending oral, multiple intravenous doses unithiol in 64 healthy adult volunteers from Kilifi County, Kenya. dose stage was informed an interim pharmacokinetic analysis, predefined target plasma concentrations. Plasma concentrations were measured using high-performance liquid chromatography-mass spectrometry, described full adverse event reporting. Findings: 175 individuals screened, (median age 30 years, IQR 25-38 years) received study drug. There no limiting toxicities or serious events. 61 solicited events, 17 related unsolicited 53 laboratory all mild moderate severity. maximum 1,500 mg well tolerated demonstrated a Cmax that equivalent to administration. Interpretation: 2 recommended (1,500 loading dose, followed 900 at 6-hours 24-hours) safe, has promising properties use. Unithiol affordable, stable room temperature, potential given orally remote rural clinics. Its further development indication warranted. Trial Registration: registered on Pan African Clinical Trials Registry (PACTR202103718625048)Funding: Wellcome Trust, Bloomsbury Set, Cures Within Reach.Declaration Interest: competing interests study.Ethical Approval: obtained ethical approval Kenya Medical Research Institute Scientific Ethics Review Unit (192/4106) Liverpool School Tropical Medicine Committee (20-032), regulatory Pharmacy Poisons Board (136). conducted accordance with requirements, including International Conference Harmonisation-Good Practice guidelines.

Language: Английский

Citations

1