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• W2168276120 abstract "I read with interest the article by Anderson et al entitled “Predicting concentrations in children presenting with acetaminophen overdose.”1Anderson BJ Holford NHG Armishaw JC Aicken R Predicting concentrations in children presenting with acetaminophen overdose.J Pediatr. 1999; 135: 290-295Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar They begin with the statement “Severe liver toxicity caused by a single dose of acetaminophen (paracetamol) elixir is rare in children 1 to 5 years.” In fact, this is true for all dosage forms of acetaminophen. On literature review, beyond two publications,2Rumack BH Acetaminophen overdose in young children. Treatment and effects of alcohol and other ingestants in 417 cases.Am J Dis Child. 1984; 138: 428-433Crossref PubMed Scopus (117) Google Scholar, 3Lieh-Lai MW Sarnaik AP Newton JF Miceli JN Fleishman LE Hook JB et al.Metabolism and pharmacokinetics of acetaminophen in a severely poisoned young child.J Pediatr. 1984; 105: 125-128Abstract Full Text PDF PubMed Scopus (55) Google Scholar one would be hard pressed to find a well-documented case of severe hepatic toxicity caused by a single dose of acetaminophen in a child 1 to 5 years old. The usual offered explanation relies upon the differences in phase II metabolism of acetaminophen between children and adults: children have a greater ratio of sulfation to glucuronidation.4Miller RP Roberts RJ Fischer LJ Acetaminophen elimination kinetics in neonates, children and adults.Clin Pharmacol Ther. 1976; 19: 284-294Crossref PubMed Scopus (266) Google Scholar However, this is illogical because it has nothing to do with the capacity to metabolize this drug. It is a qualitative rather than a quantitative difference. The generally accepted dose of concern of 150 mg/kg5Linden CH Rumack BH Acetaminophen overdose.Emerg Med Clin North Am. 1984; 2: 103-119PubMed Google Scholar was not derived from pediatric data, as these do not exist. However, the literature, the study by Anderson et al,1Anderson BJ Holford NHG Armishaw JC Aicken R Predicting concentrations in children presenting with acetaminophen overdose.J Pediatr. 1999; 135: 290-295Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar and three decades of pediatric experience with this drug indicate that children are more resistant to toxicity than adults on a milligram-per-kilogram basis. This is so because young children clear drugs more efficiently than adults. There is a simple anatomic reason for this: their livers and kidneys are larger! Maxwell6Maxwell GM Principles of pediatric pharmacology.in: Oxford University Press, New York1984: 96Google Scholar compiled data from several sources to describe the percentage of organ weight to total body weight. A few examples for the liver are: 1 year, 4%; 2 years, 3.6%; 5 years, 3%; and 18 years, 2.4%. Similar kidney values are: 1 year, 0.7%; 2 years, 0.74%; 5 years, 0.66%; and 18 years, 0.42%. Therefore the liver of a 1-year-old child is 1.67 times the size of an adult’s liver when expressed as a percentage of total body weight. Interestingly, the product of 150 mg/kg, the dose of concern derived from adult data, and 1.67 is 250 mg/kg, Anderson et al’s recommendation for a pediatric dose of concern. However, I am not comfortable with a uniform recommendation for the entire 1- to 5-year-old group because the ratio of liver weight to body weight decreases precipitously over the age range. Expressed the same way as above, the liver of a 5-year-old child is 1.25 times the size of an adult’s liver. Applying this factor in the same fashion as above (150 mg/kg × 1.25) results in a dose of concern of 187.5 mg/kg for a 5-year-old. The relatively larger liver and kidney sizes explain why larger milligramper-kilogram doses are required in children than in adults to maintain therapeutic concentrations of many drugs. Phenobarbital,7Svensmark O Buchthal F Diphenylhydantoin and phenobarbital.Am J Dis Child. 1964; 108: 82-87Crossref PubMed Scopus (105) Google Scholar, 8Eadie MJ Lander CM Hooper WD Tyrer JH Factors influencing phenobarbitone levels in epileptic patients.Br J Clin Pharmacol. 1977; 4: 541-547Crossref PubMed Scopus (55) Google Scholar phenytoin,7Svensmark O Buchthal F Diphenylhydantoin and phenobarbital.Am J Dis Child. 1964; 108: 82-87Crossref PubMed Scopus (105) Google Scholar and gentamicin9Norris S Nightingale CH Mandell GL Tables of antimicrobial agent pharmacology.in: Principles and practices of infectious diseases. Churchill Livingstone, New York1990: 446Google Scholar are but a few examples. During our training, virtually all of us endured the aphorism “children are not small adults.” Here is yet another example. 9/35/107624" @default.
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• W2168276120 title "Why young children are resistant to acetaminophen poisoning" @default.
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