Rectal paracetamol dosing regimens: determination by computer simulation

Paediatr Anaesth. 1997;7(6):451-5. doi: 10.1046/j.1460-9592.1997.d01-125.x.

Abstract

A pharmacokinetic dynamic simulation model was used to predict rectal paracetamol dosing schedules which would maintain steady state plasma concentrations of 10-20 mg.l-1. These plasma concentrations of paracetamol are known to reduce fever. The conventional dosing schedule of 15 mg.kg-1 four hourly was unsatisfactory. Steady state concentrations of 8-12 mg.l-1 were only reached after 16 h. A loading dose of 50 mg.kg-1 followed by 30 mg.kg-1 six hourly achieved plasma concentrations of 9-18 mg.l-1. Paracetamol is a mild analgesic. A higher plasma paracetamol concentration of 25 mg.l-1 is known to give satisfactory analgesia to 60% of children after tonsillectomy. This concentration can be reached after a loading dose of 70 mg.kg-1 and a maintenance dose of 50 mg.kg-1 8 hourly. Doses above 150 mg.kg-1.day-1 have been reported to cause reversible liver toxicity after 2-8 days and should not be sustained.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage*
  • Acetaminophen / adverse effects
  • Acetaminophen / blood
  • Acetaminophen / pharmacokinetics
  • Administration, Rectal
  • Adolescent
  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Non-Narcotic / adverse effects
  • Analgesics, Non-Narcotic / blood
  • Analgesics, Non-Narcotic / pharmacokinetics
  • Biological Availability
  • Child
  • Child, Preschool
  • Computer Simulation*
  • Drug Administration Schedule
  • Fever / drug therapy
  • Forecasting
  • Humans
  • Infant
  • Liver / drug effects
  • Metabolic Clearance Rate
  • Models, Biological*
  • Models, Chemical*
  • Pain, Postoperative / drug therapy
  • Suppositories
  • Tonsillectomy / adverse effects

Substances

  • Analgesics, Non-Narcotic
  • Suppositories
  • Acetaminophen