Seven of 15 clinical trial participants treated with a nucleoside analogue (fialuridine [FIAU]) developed acute liver failure. Five treated participants died, and two required a liver transplant. Preclinical toxicology studies in mice, rats, dogs, and primates did not provide any indication that FIAU would be hepatotoxic in humans. Therefore, we investigated whether FIAU-induced liver toxicity could be detected in chimeric TK-NOG mice with humanized livers.
Xu D, Nishimura T, Nishimura S, Zhang H, Zheng M, et al. (2014) Fialuridine Induces Acute Liver Failure in Chimeric TK-NOG Mice: A Model for Detecting Hepatic Drug Toxicity Prior to Human Testing. PLoS Med 11(4): e1001628. doi:10.1371/journal.pmed.1001628
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Uploaded on 17.04.2014 by
Dan Xu, Toshi Nishimura, Sachiko Nishimura, Haili Zhang et al.