bay-11-7082 and Drug-Related-Side-Effects-and-Adverse-Reactions

BAY1128688 is a selective inhibitor of AKR1C3, investigated recently in a trial that was prematurely terminated due to drug-induced liver injury. These unexpected observations prompted use of the quantitative systems toxicology model, DILIsym, to determine possible mechanisms of hepatotoxicity. Using mechanistic in vitro toxicity data as well as clinical exposure data, DILIsym predicted the potential for BAY1128688 to cause liver toxicity (elevations in serum alanine aminotransferase (ALT)) and elevations in serum bilirubin. Initial simulations overpredicted hepatotoxicity and bilirubin elevations, so the BAY1128688 representation within DILIsym underwent optimization. The liver partition coefficient K

Topics: Aldo-Keto Reductase Family 1 Member C3; Bile Acids and Salts; Bilirubin; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Humans; Liver