title: A dosing regimen for immediate N-acetylcysteine treatment for acute paracetamol overdose.
abstract: BACKGROUND
  Current treatment of paracetamol (acetaminophen) poisoning involves initiating a 3-phase N-acetylcysteine (NAC) infusion after comparing a plasma concentration, taken ≥ 4 h post-overdose, to a nomogram. This may result in dosing errors, a delay in treatment, or possibly more adverse effects - due to the use of a high dose rate for the first infusion when treatment is initiated.
  
  
  OBJECTIVE
  Our aim was to investigate a novel dosing regimen for the immediate administration of NAC on admission at a lower infusion rate.
  
  
  METHODS
  We used a published population pharmacokinetic model of NAC to simulate a scenario where a patient presents to the hospital 2 h post-overdose. The conventional regimen is commenced 6 h post-overdose when the 4-h plasma paracetamol concentration is available. We investigated an NAC infusion using a lower dosing rate initiated immediately on presentation. We determined a dosing rate that gave an area under the curve (AUC) of the concentration-time curve that was the same or greater than that from the conventional regimen on 90% of occasions.
  
  
  RESULTS
  Lower dosing rates of NAC initiated immediately resulted in a similar exposure to NAC. An infusion of 110 mg/kg over the first 5 h (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 h (22.6 mg/kg/h) followed by the last phase of the conventional regimen could be used.
  
  
  CONCLUSIONS
  The novel dosing regimen allowed immediate treatment of a patient using a lower dosing rate. This greatly simplifies the current dosing regimen and may reduce NAC adverse effects while ensuring the same amount of NAC is delivered.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Finna
authors.initials: F
authors.lastname: Shen
authors.forename: Carolyn V
authors.initials: CV
authors.lastname: Coulter
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics / Q000506:poisoning*; D000111:Acetylcysteine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000328:Adult; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000506:poisoning*; D000931:Antidotes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D003198:Computer Simulation; D004334:Drug Administration Schedule; D062787:Drug Overdose / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D008954:Models, Biological
chemical_list: D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D000975:Antioxidants; D000082:Acetaminophen; D000111:Acetylcysteine