Paracetamol, also known as acetaminophen, is a widely used analgesic and antipyretic drug. It undergoes metabolism in the liver through three primary pathways: glucuronidation, sulfation, and oxidation. The majority of paracetamol is metabolized via glucuronidation and sulfation, while a small portion undergoes oxidation.1. Glucuronidation: This is the primary metabolic pathway for paracetamol, accounting for 50-70% of the drug's metabolism. In this process, paracetamol is conjugated with glucuronic acid by the enzyme UDP-glucuronosyltransferase UGT . This reaction forms paracetamol glucuronide, which is a water-soluble and non-toxic metabolite that can be easily excreted in the urine.2. Sulfation: This pathway accounts for 20-30% of paracetamol metabolism. Paracetamol is conjugated with a sulfate group by the enzyme sulfotransferase SULT , forming paracetamol sulfate. This metabolite is also water-soluble and non-toxic, allowing for easy excretion in the urine.3. Oxidation: A small portion of paracetamol 5-10% undergoes oxidation by the cytochrome P450 enzyme system, specifically CYP2E1, CYP1A2, and CYP3A4. This process generates a reactive and toxic intermediate metabolite called N-acetyl-p-benzoquinone imine NAPQI . Under normal circumstances, NAPQI is rapidly detoxified by conjugation with glutathione, forming a non-toxic cysteine or mercapturic acid conjugate, which can be excreted in the urine. However, if the glutathione stores in the liver are depleted, NAPQI can accumulate and cause hepatotoxicity by binding to cellular proteins and causing oxidative stress, leading to liver damage.In summary, paracetamol is primarily metabolized in the liver through glucuronidation, sulfation, and oxidation. The main metabolites formed are paracetamol glucuronide, paracetamol sulfate, and NAPQI which is further detoxified by glutathione . The first two metabolites are non-toxic and easily excreted, while NAPQI can cause hepatotoxicity if not adequately detoxified.