No abstract is available for this article. more
To use all functions of this page, please activate cookies in your browser.
My watch list
my.bionity.com
my.bionity.com
With an accout for my.bionity.com you can always see everything at a glance – and you can configure your own website and individual newsletter.
- My watch list
- My saved searches
- My saved topics
- My newsletter
Dose‐dependent acute liver injury with hypersensitivity features in humans due to a novel microsomal prostaglandin E synthase 1 inhibitor
Summary Aim
LY3031207, a novel microsomal prostaglandin E synthase 1 inhibitor, was evaluated in a multiple ascending dose study after nonclinical toxicology studies and a single ascending dose study demonstrated an acceptable toxicity, safety, and tolerability profile.
MethodsHealthy subjects were randomised to receive LY3031207 (25, 75, and 275 mg), placebo, or celecoxib (400 mg) once daily for 28 days. The safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of LY3031207 were evaluated.
ResultsThe study was terminated when two subjects experienced drug‐induced liver injury (DILI) after they had received 225 mg LY3031207 for 19 days. Liver biopsy from these subjects revealed acute liver injury with eosinophilic infiltration. Four additional DILI cases were identified after LY3031207 dosing had been stopped. All six DILI cases shared unique presentations of hepatocellular injury with hypersensitivity features and demonstrated a steep dose‐dependent trend. Prompt discontinuation of the study drug and supportive medical care resulted in full recovery. Metabolites from metabolic activation of the imidazole ring were observed in plasma and urine samples from all subjects randomized to LY3031207 dosing.
ConclusionsThis study emphasised the importance of careful safety monitoring and serious adverse events management in phase I trials. Metabolic activation of the imidazole ring may be involved in the development of hepatotoxicity of LY3031207.
| Authors: | Yan Jin, Arie Regev, Jeanelle Kam, Krista Phipps, Claire Smith, Judith Henck, Kristina Campanale, Leijun Hu, D. Greg Hall, Xiao Yan Yang, Masako Nakano, Terry Ann McNearney, Jack Uetrecht, William Landschulz | |
| Journal: | British Journal of Clinical Pharmacology | |
| Year: | 2017 | |
| Pages: | n/a | |
| DOI: | 10.1111/bcp.13423 | |
| Publication date: | 02-Sep-2017 |
Facts, background information, dossiers
More about Wiley
-
Publications
Standardisation of inactivated influenza vaccines – learning from history
Abstract The single radial immunodiffusion assay has been the accepted method for determining the potency of inactivated influenza vaccines since 1978. The world‐wide adoption of this assay for vaccine standardisation was facilitated through collaborative studies that demonstrated a high ... more
1918 pandemic morbidity: the first wave hits the poor, the second wave hits the rich
Abstract Background Whether morbidity from the 1918‐19 influenza pandemic discriminated by socioeconomic status has remained a subject of debate for 100 years. In lack of data to study this issue recent literature have hypothesized that morbidity was “socially neutral”. Objectives ... more
-
News
Smart skin made of recyclable materials may transform medicine and robotics
Smart skin that can respond to external stimuli could have important applications in medicine and robotics. Using only items found in a typical household, researchers have created multi-sensor artificial skin that's capable of sensing pressure, temperature, humidity, proximity, pH, and air ... more
Acetaminophen provides no benefits against the flu
Some doctors may recommend that patients with the flu take acetaminophen, or paracetemol, to relieve their symptoms; however, a new randomized clinical trial found no benefits to the over-the-counter medication in terms of fighting the influenza virus or reducing patients' temperature or ot ... more
Study identifies psychological traits associated with homophobia
A new study that investigated the potential of certain psychological traits for predisposing heterosexuals to have negative attitudes towards homosexual people found that psychoticism - which is present in severe psychopathological conditions but may also contribute to less severe states of ... more
Meistgelesene Fachpublikationen
- 1[Report] Mouse B-Type Lamins Are Required for Proper Organogenesis But Not by Embryonic Stem Cells
- 2Development of high‐quality weaning food based on maize and chickpea by twin‐screw extrusion process for low‐income populations
- 3Particle Size Distribution of Brown and White Rice during Gastric Digestion Measured by Image Analysis
- 4Anti-Inflammatory Effects of Acupuncture Stimulation via the Vagus Nerve
- 5Effect of crosslinking on the performance of a collagen‐derived biomaterial as an implant for soft tissue repair: A rodent model
- 6Polycaprolactone fiber meshes provide a 3D environment suitable for cultivation and differentiation of melanocytes from the outer root sheath of hair follicle
- 7Effect of Continuous Ohmic Heating to inactivate Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes in Orange and Tomato Juice
- 8Comparative Antibacterial Activity of Tryptic‐Hydrolyzed Palm Kernel Cake Proteins of Different Degrees of Hydrolysis
- 9Bioengineering: Cell culture on a chip
- 10Chitosan-hyaluronan based 3D co-culture platform for studying the crosstalk of lung cancer cells and mesenchymal stem cells
