Glucosamine enhances paracetamol bioavailability by reducing its metabolism

Paracetamol has an extensive first-pass metabolism that highly affects its bioavailability (BA); thus, dose may be repeated several times a day in order to have longer efficacy. However, hepatotoxicity may arise because of paracetamol metabolism. Therefore, this project aimed to increase paracetamol BA in rats by glucosamine (GlcN). At GlcN-paracetamol racemic mixture ratio of 4:1 and paracetamol dose of 10 mg/kg, paracetamol area under the curve (AUC) and maximum concentration (Cmax ) were significantly increased by 99% and 66%, respectively (p < 0.05). Furthermore, paracetamol AUC and Cmax levels were increased by 165% and 88% in rats prefed with GlcN for 2 days (p < 0.001). Moreover, GlcN significantly reduced phase Ι and phase I/ΙΙ metabolic reactions in liver homogenate by 48% and 54%, respectively. Furthermore, GlcN molecule was found to possess a good in silico binding mode into the CYP2E1 active site-forming bidentate hydrogen bonding with the Thr303 side chain. Finally, serum ALT and AST levels of rats-administered high doses of paracetamol were significantly reduced when rats were prefed with GlcN (p < 0.01). In conclusion, GlcN can increase the relative BA of paracetamol through reducing its metabolism. This phenomenon is associated with reduction in hepatocytes injury following ingestion of high doses of paracetamol.