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Arun Parashar*


Background: Besides being the most widely consumed drug, paracetamol is also the leading cause for hepatic failure in many of the western countries. According to the USFDA acute overdoses of paracetamol can cause potentially serious liver damage. Objective: This study aimed toward designing and evaluating a safer analog (in terms of hepatotoxicity) of paracetamol in the form of a prodrug. The prodrug was evaluated for the proverbial therapeutic effects of paracetamol i.e. analgesic & antipyretic, together with gastric lesion healing and hepatotoxicity studies. Prodrug was given to animals in a dose molecularly equivalent to that of paracetamol. The dose was calculated using molecular weight of paracetamol and the prodrug. Methodology: Paracetamol prodrug was synthesized by esterification between carboxyl group of amino acid and hydroxyl group of paracetamol. Analgesic, antipyretic, ulcer healing and hepatotoxic activities were performed in this study. Results: Prodrug showed a 36% inhibition in writhings as compared to 53.3% of paracetamol. Maximum antipyretic effect was observed 3 hours after the drug administration. Fever reduction was greater in paracetamol group. Prodrug showed excellent gastroprotective effects as it reduced the gastric lesions by 20.3%. The prodrug exhibited a hepatoprotective effect by preventing the rise in liver enzymes (SGOT, SGPT and bilirubin). The most notable effect of prodrug was in preventing the fall of hepatic glutathione (GSH) levels as it is one of the major antioxidant of our body. Conclusion: Prodrug showed excellent hepatoprotective and gastroprotective effects, although it’s therapeutic efficacy was compromised.

Keywords: Paracetamol, Prodrug, Hepatotoxicity, Amino acid, Alanine.

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