Initial and subsequent dosing of rectal acetaminophen in children - A 24-hour pharmacokinetic study of new dose recommendations

Background: Recent studies have determined that an initial rectal acetamino phen dose of approximately 40 mg/kg is needed in children to achieve target antipyretic serum concentrations. The timing and amount of subsequent dose s after a 40-mg/kg dose has not been clarified for this route of administra tion. Based on the authors' previous pharmacokinetic data, they examined wh ether a 40-mg/kg loading dose followed by 20-mg/kg doses at 6-h intervals m aintain serum concentrations within the target range of 10-20 mug/ml, witho ut evidence of accumulation. Methods: Children (n = 16) received rectal acetaminophen (40 mg/kg) and up to three additional doses of 20 mg/kg at 6-h intervals. Venous blood sample s were taken every 30 min for 4 h, then every 60 min for 4 h, and every 4 h for 16 h. The authors assessed whether their published pharmacokinetic par ameters predicted the acetaminophen concentrations in the present study. Th ey also assessed their dosing regimen by determining the fraction of time e ach individual maintained the target concentration. Results: All patients received the initial loading dose; 10 of 16 patients received three subsequent doses. Serum concentrations with the initial dose were in the target range 38 +/- 25% of the time. With subsequent dosing, t he target range was maintained 60 +/- 29% of the time. The highest serum co ncentration with initial or subsequent dosing was 38.6 mug/ml. Pharmacokine tic parameters from the earlier study predicted the serum concentrations ob served for both initial and subsequent doses. Conclusions: A rectal acetaminophen loading dose of 40 mg/kg followed by 20 -mg/kg doses every 6 h results in serum concentrations centered at the targ et range of 10-20 mug/ml. There was large interindividual variability in ph armacokinetic characteristics. There was no evidence of accumulation during the 24-h sampling period.