Summary
Acetaminophen serum concentrations were studied in 21 infants and children with fever. The maximum serum concentrations ranged from 9.96 to 19.6 µg/ml after a single dose of 12–14 mg/kg and 13.9 to 40.1 µg/ml after a single dose of 22–27 mg/kg. Ten patients were restudied at steadystate 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<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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blaschke TF, Elin RJ, Berk PD, Song CS, Wolff SM (1973) Effect of fever on sulfo-bromophtalein kinetics in man. Ann Intern Med 78: 221–226
Elin RJ, Vesell ES, Wolff SM (1975) Effects of etiocholanolone-induced fever on plasma antipyrine half-lives and metabolic clearance. Clin Pharmacol Ther 17: 447–457
Galinsky RE, Levy G (1981) Dose- and time-dependent elimination of acetaminophen in rats: pharmacokinetic implications of cosubstrate depletion. J Pharmacol Exp Ther 219: 24–30
Gibaldi M, Perrier D (1982) Pharmacokinetics, 2nd edn. Marcel Dekker, New York
Howie D, Adriaenssens PI, Prescott LF (1977) Paracetamol metabolism following overdosage: application of high performance liquid chromatography. J Pharm Pharmacol 29: 235–237
Miller RP, Roberts RJ, Fisher LF (1976) Acetaminophen elimination kinetics in neonates, children and adults. Clin Pharmacol Ther 19: 284–294
Mitchell AA, Lovejoy FH, Slone D, Shapiro S (1982) Acetaminophen and aspirin. Am J Dis Child 136: 976–979
Rumack BH, Matthew H (1975) Acetaminophen poisoning and toxicity. Pediatrics 55: 871–873
Slatery JT, Levy G (1979) Acetaminophen kinetics in acutely poisoned patients. Clin Pharmacol Ther 25: 184–195
Trenholme GM, Williams RL, Rieckmann KH, Frischer H, Carson PE (1976) Quinine disposition during malaria and during induced fever. Clin Pharmacol Ther 19: 459–467
Wilson JT, Brown RD, Bocchini JA, Kearns GL (1982) Efficacy, disposition and pharmacodynamics of aspirin, acetaminophen and choline salicylate in young febrile children. Ther Drug Monit 4: 147–180
Windorfer A, Vogel C (1976) Investigations of the serum concentrations and temperature curves following the administration of a new oral fluid preparation of paracetamol. Clin Pediatr 188: 430
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Nahata, M.C., Powell, D.A., Durrell, D.E. et al. Acetaminophen accumulation in pediatric patients after repeated therapeutic doses. Eur J Clin Pharmacol 27, 57–59 (1984). https://doi.org/10.1007/BF02395207
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02395207