Acetaminophen accumulation in pediatric patients after repeated therapeutic doses

Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 micrograms/ml after a single dose of 12-14 mg/kg and 13.9 to 40.1 micrograms/ml after a single dose of 22-27 mg/kg. Ten patients were restudied at steady-state after repeat doses had been given every 4 or 8 h for 1 to 3 days. Total area under the acetaminophen serum concentration-time curve normalized for dose averaged 0.181 (ml/min/kg)-1 after the first dose and 0.202 (ml/min/kg)-1 at steady-state (p less than 0.05). Five patients showed a 13 to 44% increase in the AUC; one had a 10% decrease in the AUC; and four had less than 6% change in the AUC. There was no evidence of hepatotoxicity. These data suggest that acetaminophen may accumulate after repeated therapeutic doses in children with fever.