After oral administration it is rapidly absorbed by the GI tract; its volume of distribution is roughly 50 L.[14]
Paracetamol is metabolised primarily in the liver, into toxic and non-toxic products. Three metabolic pathways are notable:[69]
Glucuronidation (45-55%)[3]
Sulfation (sulfate conjugation) accounts for 20–30%.[3]
N-hydroxylation and dehydration, then GSH conjugation, accounts for less than 15%. The hepatic cytochrome P450 enzyme system metabolises paracetamol, forming a minor yet significant alkylating metabolite known as NAPQI (N-acetyl-p-benzoquinone imine)(also known as N-acetylimidoquinone).[69][98] NAPQI is then irreversibly conjugated with the sulfhydryl groups of glutathione.[98]
All three pathways yield final products that are inactive, non-toxic, and eventually excreted by the kidneys. In the third pathway, however, the intermediate product NAPQI is toxic. NAPQI is primarily responsible for the toxic effects of paracetamol; this constitutes an example of toxication.[99] Production of NAPQI is due primarily to two isoenzymes of cytochrome P450: CYP2E1 and CYP3A4.[99] At usual doses, NAPQI is quickly detoxified by conjugation with glutathione