ArticlePharmaceutical research2017
Evaluation of the Utility of Chimeric Mice with Humanized Livers for the Characterization and Profiling of the Metabolites of a Selective Inhibitor (YM543) of the Sodium-Glucose Cotransporter 2.
Article in Pharmaceutical research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
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1 author.
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Abstract
purposeYM543 is a novel selective inhibitor of the sodium-glucose cotransporter 2. The objectives of the current study were to evaluate the utility of mice with humanized livers to predict human drug metabolites using YM543 as a case example.
methodsMetabolites of YM543 generated in humans and experimental animals including chimeric mice with humanized liver, PXB mice, were analyzed via liquid chromatography-mass spectrometry, liquid chromatography-radiometric detector or nuclear magnetic resonance spectrometer.
resultsAfter oral administration of YM543, metabolites M1-M5 were detected in human plasma and urine. M2-M4 were detected in at least one species while M1 was not generated by experimental animals or in vitro systems. In the metabolite profiling in PXB mice, M1 was detected in both plasma and urine samples.
conclusionsMetabolite profile of YM543 in PXB mice and humans was closely resemble. and the human specific metabolite was detected in the model mice. The human specific metabolite, M1, was difficult to know in advance to clinical study. The ability to predict the human metabolite profile including presence of human specific metabolites using PXB mice will likely facilitate development of new drug candidates for human use.
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