ArticleEuropean journal of clinical pharmacology2017
Pharmacokinetic modelling of modified acetylcysteine infusion regimens used in the treatment of paracetamol poisoning.
Article in European journal of clinical pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 14 citations in OpenAlex.
- Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose (2NAC study).EClinicalMedicine · 2020Article
- Medicinal Thiols: Current Status and New Perspectives.Mini reviews in medicinal chemistry · 2020Review
- Article
- In reply.European journal of clinical pharmacology · 2018Article
- In response to: "Pharmacokinetic modelling of modified acetylcysteine infusion regimens used in the treatment of paracetamol poisoning".European journal of clinical pharmacology · 2018Article
Corrections and comments
- Commented on byIn reply.2018
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeParacetamol overdose is common and is treated with acetylcysteine to prevent the development of hepatotoxicity. N-acetyl-p-benzoquinone imine (NAPQI) is the toxic metabolite of paracetamol overdose. We aimed to assess the expected acetylcysteine concentration time profiles following delivery of modified acetylcysteine regimens proposed for those at high and low risk of hepatotoxicity. In addition, we will determine acetylcysteine concentrations post-cessation of abbreviated infusions.
methodWe performed pharmacokinetic simulations using Berkeley Madonna (version 8.3.23.0) comparing the time course of acetylcysteine concentration during and after the cessation of an abbreviated 12-h regimen (250 mg/kg) using a two-bag infusion and compared this to the standard 21-h three-bag (300 mg/kg) regimen. We also simulated extended duration acetylcysteine regimens and other increased dosing strategies that have been recommended in specific paracetamol poisoning scenarios.
resultsA more sustained serum concentration is achieved when the acetylcysteine loading dose is delivered over 4 h using the two-bag compared to the 1-h loading dose of the three-bag regimen. When administering an abbreviated 12-h acetylcysteine regimen, circulating acetylcysteine is detectable for 8 h after cessation of the infusion. This may provide a continued hepatoprotective effect if NAPQI is still being generated after the infusion is ceased.
conclusionThis pharmacokinetic simulation study is an important step in determining plasma acetylcysteine concentrations that are likely to be achieved using various modified treatment regimens. Importantly, for patients at low risk of liver injury after acute overdose, acetylcysteine is likely to be detectable many hours post-cessation of a 12-h regimen. This should provide a safety factor against development of hepatotoxicity for any ongoing paracetamol metabolism after cessation of the acetylcysteine infusion.
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