title: Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.
abstract: OBJECTIVE
  Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL).
  
  
  METHODS
  A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range.
  
  
  RESULTS
  The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child).
  
  
  CONCLUSIONS
  With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.
authors.affiliation: From the *Division of Emergency Medicine, University of Toronto, Toronto, ON; †Department of Medicine, McGill University, McGill University Health Center; ‡Emergency Department, Montreal General Hospital, §Pharmacy Department, McGill University Health Center, Montréal, QC; and ||Department of Emergency Medicine and Toxicology, McGill University Health Center, Royal Victoria Hospital, Montreal, Quebec, Canada.
authors.forename: Daniel Asher
authors.initials: DA
authors.lastname: Abourbih
authors.forename: Sophie
authors.initials: S
authors.lastname: Gosselin
authors.forename: Eric
authors.initials: E
authors.lastname: Villeneuve
authors.forename: Sara
authors.initials: S
authors.lastname: Kazim
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000367:Age Factors; D058633:Antipyretics / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008297:Male; D008954:Models, Biological; D010372:Pediatrics / Q000379:methods
chemical_list: D058633:Antipyretics; D000082:Acetaminophen