Chlorzoxazone reduced the paracetamol-induced toxicity via competitive inhibition of CYP2E1-mediated metabolism

Abstract Background Drug metabolism is crucial to attaining the therapeutic index of any drug. The and elimination drugs are governed mainly by P-glycoprotein (P-gp) Cytochrome P450 (CYP). Paracetamol mostly used as analgesic antipyretic agent. paracetamol primarily via Glucuronidation sulphation at doses. About 5–10% metabolized CYP mediated pathway. 2E1 (CYP2E1) responsible for forming a toxic metabolite called N -acetyl- p -benzoquinoneimine (NAPQI). Even doses, long-term usage leads hepatic nephrotoxicity because NAPQI. Several in-vitro in-vivo studies conducted different research groups reported that chlorzoxazone substrate inhibitor CYP2E1. However, effect on (CYP2E1 substrate) CYP2E1 has not yet been reported. This study investigated CYP2E1-mediated NAPQI formation in Wistar rats. Results For 15 days, animals were orally administered with (300 mg/kg) without Silymarin (100 (standard inhibitor) Chlorzoxazone (50 100 mg/kg). Analysis was performed using RP-HPLC 15th day determine concentration plasma. combination showed dose-dependent increase AUC 0–∞ peak plasma (C max ) decrease C compared control ( < 0.001). significantly decreased elevated liver renal markers control. Simultaneously, Hepatic nephrotic tissue group, ameliorated paracetamol-induced hepatotoxicity nephrotoxicity. Conclusion Finally, this revealed led significant levels enhanced absorption rats inhibition CYP2E1- metabolism. In addition,