Characterization of Fasiglifam-Related Liver Toxicity in Dogs
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چکیده
منابع مشابه
Fasiglifam (TAK-875) Inhibits Hepatobiliary Transporters: A Possible Factor Contributing to Fasiglifam-Induced Liver Injury.
Fasiglifam (TAK-875), a selective G-protein-coupled receptor 40 agonist, was developed for the treatment of type 2 diabetes mellitus; however, its development was terminated in phase III clinical trials because of liver safety concerns. Our preliminary study indicated that intravenous administration of 100 mg/kg of TAK-875 increased the serum total bile acid concentration by 3 to 4 times and to...
متن کاملFasiglifam (TAK-875) Alters Bile Acid Homeostasis in Rats and Dogs: A Potential Cause of Drug Induced Liver Injury
Fasiglifam (TAK-875), a Free Fatty Acid Receptor 1 (FFAR1) agonist in development for the treatment of type 2 diabetes, was voluntarily terminated in phase 3 due to adverse liver effects. A mechanistic investigation described in this manuscript focused on the inhibition of bile acid (BA) transporters as a driver of the liver findings. TAK-875 was an in vitro inhibitor of multiple influx (NTCP a...
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Xylitol, a sugar substitute used in sugar-free gum, oral care products, and baked goods, is gaining popularity in the United States. Xylitol consumption is considered harmless to people but is known to cause life-threatening toxicoses in dogs. Dogs that ingest doses of >0.1 g/kg of xylitol are at risk for developing hypoglycemia, while dogs that ingest >0.5 g/kg may develop acute liver failure....
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ژورنال
عنوان ژورنال: Drug Metabolism and Disposition
سال: 2019
ISSN: 0090-9556,1521-009X
DOI: 10.1124/dmd.118.084889