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 parac etamol are known to reduce fever. The conventional dosing schedule of 15 mg.kg(-1) four hourly was unsatisfactory. Steady state concentratio ns 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 concent rations of 9-18 mg.l(-1) Paracetamol is a mild analgesic. A higher pla sma paracetamol concentration of 25 mg.l(-1) is known to give satisfac tory analgesia to 60% of children after tonsillectomy. This concentrat ion can be reached after a loading dose of 70 mg.kg(-1) and a maintena nce dose of 50 mg.kg(-1) 8 hourly. Doses above 150 mg.kg(-1).day(-1) h ave been reported to cause reversible liver toxicity after 2-8 days an d should not be sustained.