Mouse Model I. Nassar 1 , T. Pasupati 1 , I. Segarra 1 , J.P. Judson 1 1 International Medical University, Kuala Lumpur, Malaysia Background: Imatinib, a selective tyrosine kinase inhibitor, exhibits drug interactions with other drugs that are metabolised via the cytochrome P450 pathway. Acetaminophen, a widely used analgesic and anti-pyretic drug is also metabolised via P450 pathway. This study aimed to evaluate the nature of hepatotoxicity after co-administration of imatinib and acetaminophen in a preclinical mouse model. Methods: Four groups of male ICR mice (30-35g) were used. The mice were administered either saline solution orally, imatinib 100 mg/kg orally (control), acetaminophen 700 mg/kg intraperitoneally (positive control) or co-administered imatinib 100 mg/kg and IP acetaminophen 700 mg/kg (study group). The mice (n=4 per group) were fasted overnight, dosed respectively and sacrificed at pre-determined time intervals of 15, 30 minutes, 1, 2, 4, 9 and 12 hours and liver samples obtained by dissection. H&E stained liver sections (3µm thick) were histopathologically analysed. Results: The liver samples showed reversible cell damage like feathery degeneration, microvesicular fatty change, sinusoidal congestion and pyknosis, with both imatinib and acetaminophen, administered separately.