Paracetamol is commonly used as a first choice analgesic
for different nociceptive acute or chronic pain and remains
one of the safest available analgesics. However, the
use of this drug in patients with hepatic disease is often
avoided. This perception arose from awareness of hepatotoxic
effect of paracetamol overdose and a lack of understanding
its metabolic pathway in patients with liver
disease. It is known that the majority of paracetamol is
metabolized via the sulfation and glucuronidation pathways
into nontoxic products which are then excreted via
the urine. However, a small proportion (< 5%) is oxidized
via CYP system, mostly CYP2E1, to a hepatotoxic intermediate,
N-acetyl-p-benzoquinone imine (NAPQI), which is
readily rendered nontoxic by conjugation to glutathione
(17). Pharmacokinetic studies have indicated an increase
in the elimination half-life (t ½) of paracetamol in patients
with liver cirrhosis compared with healthy controls.
Meanwhile, the plasma clearance of the drug was
shown to be reduced in these patients (18-20). However,
the t ½ of the drug or its plasma clearance has been found
to be correlated with prothrombin time as well as the
plasma albumin levels.