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Abstract

SYNTHESIS AND BIOEVALUATION OF ALKYL DERIVATIVES AND PRODRUG OF PARACETAMOL TO REDUCE HEPATOTOXICITY

Shalini Kesharwani*, Dr. Arun Patel, Shailendra Patel and Neelesh Dwivedi

ABSTRACT

Paracetamol, the most commonly used analgesic – antipyretic drug, damage multiple organs. The half life of Paracetamol is 1- 4 h which is very less and thus given in repeated high dose (Daily dose : 1000 mg per single dose and up to 4000 mg per day for adults). This lead to higher toxicity especially in liver and kidney. The toxicity of paracetamol is due to its metabolites, N-acetyl-p-benzoquinoneimine. Paracetamol overdose leads to the accumulation of NAPQI, which undergoes conjugation with glutathione. Conjugation depletes glutathione, a natural antioxidant. This directed cellular injury by NAPQI, leads to cell damage cause hepatotoxicity and even death. The formation of NAPQI can be minimized by reducing metabolism by CYP-450 which can be achieved by derivatization of paracetamol and also supplying a precursor of glutathione with drug reduced depletion of glutathione.

Keywords: Paracetamol, Alkyl Derivatives, Prodrug, N-acetyl-p-benzoquinoneimine, glutathione.


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