P11-02 The human quad-culture liver-chip differentiates toxicity of trovafloxacin from Levofloxacin

摘要: Purpose: Immune-mediated drug-induced liver injury (I-DILI) is a drug-specific adverse response, which is difficult to predict preclinically but becomes evident in clinical trials, thereby leading to failures and recalls [1]. Thus, to better understand these mechanisms and overcome the limitations set forth by traditional cell culture systems, Organ-Chip technology was used to confirm the toxicity of trovafloxacin which was withdrawn from the market due to DILI and the lesser toxic levofloxacin. Acetaminophen was used as a positive control.Methods: Forty-six Human Quad-Culture Liver-Chips (Emulate Inc.), were prepared with primary human hepatocytes and liver non-parenchymal cells including liver sinusoidal endothelial cells, Kupffer cells, and stellate cells. After 7 days in culture, Liver-Chipswere treated with acetaminophen (0.3, 1, 3, or 10 mM), trovafloxacin, or levofloxacin (both at 4, 30 or, 200 µM) for a further 14 …