Rectal paracetamol dosing regimens: determination by computer simulation

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.