Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2014 Publisher: Phoenix Labs, Suite 12, Bunkilla Plaza, Bracetown Business Park, Clonee, Co. Meath, Ireland
Acetylcysteine is considered to reduce the hepatic toxicity of NAPQI (n-acetyl-p-benzo-quinoneimine), the highly reactive intermediate metabolite following ingestion of a high dose of paracetamol, by at least two mechanisms. First, acetylcysteine acts as a precursor for the synthesis of glutathione and, therefore, maintains cellular glutathione at a level sufficient to inactivate NAPQI. This is thought to be the main mechanism by which acetylcysteine acts in the early stages of paracetamol toxicity.
Acetylcysteine has been shown to still be effective when infusion is started at up to 12 hours after paracetamol ingestion, when most of the analgesic will have been metabolised to its reactive metabolite. At this stage, acetylcysteine is thought to act by reducing oxidised thiol groups in key enzymes.
When acetylcysteine treatment is begun more than 8 to 10 hours after paracetamol overdose, its efficacy in preventing hepatotoxicity (based on serum indicators) declines progressively with further lengthening of the overdose-treatment interval (the time between paracetamol overdose and start of treatment). However, there is now evidence that it can still be beneficial when given up to 24 hours after overdose. At this late stage of paracetamol hepatotoxicity, acetylcysteine’s beneficial effects may be due to its ability to improve systematic haemodynamics and oxygen transport, although the mechanism by which this may occur has yet to be determined.
Following intravenous administration of acetylcysteine using the standard 20-hour intravenous regimen, plasma levels of 300 to 900mg/l have been reported to occur shortly after the start of the infusion, falling to 11 to 90mg/l at the end of the infusion period. Elimination half-lives of 2 to 6 hours have been reported after intravenous dosing, with 20 to 30% of the administered dose being recovered unchanged in the urine.
Metabolism appears to be rapid and extensive. There is no information on whether acetylcysteine crosses the blood-brain barrier or the placenta, or whether it is excreted in breast milk.
None stated.
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