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Four-hour acetaminophen concentration estimation after ingested dose based on pharmacokinetic models.

E Villeneuve1, S Gosselin, I Whyte

  • 1Department of Pharmacy, McGill University Health Centre , Montreal, QC , Canada.

Clinical Toxicology (Philadelphia, Pa.)
|April 5, 2014
PubMed
Summary

The UK

Keywords:
Poison centerPoisoningReferral dose

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Area of Science:

  • Pharmacokinetics and Toxicology
  • Drug Overdose Management

Background:

  • Recent UK guideline changes for acetaminophen (paracetamol) overdose treatment.
  • New UK guideline: any ingestion >75 mg/kg warrants hospital referral.
  • Lack of evidence-based guidance for current acetaminophen referral criteria.

Purpose of the Study:

  • To develop a pharmacokinetic model predicting 4-hour acetaminophen concentrations.
  • To evaluate current UK acetaminophen ingestion referral guidelines.
  • To compare predicted concentrations with established treatment lines.

Main Methods:

  • Systematic literature search (EMBASE, Medline) for acetaminophen pharmacokinetic parameters.
  • Calculation of 4-hour plasma acetaminophen concentrations for various ingestion doses.
  • Comparison of calculated concentrations against Rumack-Matthew and UK treatment lines.

Main Results:

  • Calculated doses required for a 4-hour acetaminophen concentration of 100 mg/L: 180.5 mg/kg (adults) and 396.1 mg/kg (children).
  • A 75 mg/kg ingestion dose is predicted to result in concentrations well below 100 mg/L at 4 hours.
  • Data derived from 6 studies (4 adult, 2 pediatric).

Conclusions:

  • Current UK referral guidelines for acetaminophen overdose may lack sufficient evidence.
  • Existing guidelines do not provide clear criteria for hospital referral based on ingestion history.
  • Need for larger toxicokinetic studies to establish evidence-based acetaminophen overdose referral criteria.