The Metabolism of Liver Cancer Treatment Drug Sorafenib is Affected by Acetaminophen Treatment

Sorafenib is a commonly used drug for the treatment of liver cancer, and sorafenib has high possibility to co-administration with acetaminophen (APAP) which has been frequently used in the clinic. The present study aims to evaluate the metabolic behavior in acetaminophen-treated mice. Intraperitoneal injection with 500 mg/kg body weigh of APAP was employed to induce the liver damage. The results showed APAP treatment resulted in the alter histology of liver, and increased activity of of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Western blotting analysis showed that APAP treatment can decrease the expression of drug-metabolizing enzymes cytochrome P450 (CYP) 3A4 and UDP-glucuronosyltransferase (UGT) 1A9, which furtherly weakened the oxidation and glucuronidation metabolism of sorafenib. In conclusion, the metabolism of sorafenib was significantly decreased in acetaminophen-treated mice, which guiding the clinical application of acetaminophen and sorafenib.