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One Response to “What Is The Important Physicochemical Property Of Paracetamol + How Does That Influence Route Of Elimination?”

1. Slippery says:

   June 29, 2009 at 7:06 am

   Paracetomol is soluble in organic solvents such as methanol and ethanol but is only sligtly soluble in water. The resulting glucuronide has a much higher water solubility than the original substance and is eventually excreted.
   Paracetamol is metabolized primarily in the liver, where most of it (60-90% of a therapeutic dose) is converted to inactive compounds by conjugation with sulfate and glucuronide, and then excreted by the kidneys. Only a small portion (5-10% of a therapeutic dose) is metabolized via the hepatic cytochrome P450 enzyme system (specifically CYP2E1); the toxic effects of paracetamol are due to a minor alkylating metabolite (N-acetyl-p-benzo-quinone imine, abbreviated as NAPQI) that is produced through this enzyme, not paracetamol itself or any of the major metabolites. The metabolism of paracetamol is an excellent example of toxication, because the metabolite NAPQI is primarily responsible for toxicity rather than paracetamol itself.
   Glucuronidation is the process of chemically binding a substance to glucuronic acid via a glycosidic bond. The resulting glucuronide is typically much more water soluble than the original substance. The human body uses glucuronidation to excrete a large variety of molecules, including drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids and bile acids. Most of this is done by the liver.
   At usual doses, the toxic metabolite NAPQI is quickly detoxified by combining irreversibly with the sulfhydryl groups of glutathione to produce a non-toxic conjugate that is eventually excreted by the kidneys.