Pharmacokinetics of rectal paracetamol after repeated dosing in children

Twenty-three children (aged between 9 weeks and 11 yr) were given paracetam ol suppositories 25 mg kg(-1) every 6 h (maximum 5 days) after major surger y and serum and saliva concentrations were measured. There was a good corre lation (r=0.91, P<0.05) between saliva and serum concentrations. A one-comp artment linear model with first-order elimination and absorption and lag-ti me was fitted to the data (ADAPT II). At steady state, the mean (SD) concen tration was 15.2 (6.8) mg litre(-1). Mean (SD) time to reach 90% of the ste ady state concentration was 11.4 (8.6) h. Body weight, age and body surface area were well correlated (P<0.05) with clearance and apparent volume of d istribution. There was no evidence of accumulation leading to supratherapeu tic concentrations during this dosing schedule for a mean of approximately 2-3 days.