Acetaminophen in cerebrospinal fluid in children

Eur J Clin Pharmacol. 2003 Aug;59(4):297-302. doi: 10.1007/s00228-003-0622-2. Epub 2003 Jul 4.


Background: There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in children--from neonates to adolescents--in order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP.

Methods: Children (n=41) 1 week to 18 years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 30-40 mg/kg APAP 1 h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric "1/4 power models".

Results: Median (25-75th percentile) age and weight of the patients included in this study were 12 months (3-62 months) and 10.0 kg (5.8-20.0 kg). Median (25-75th percentile) time between APAP loading dose administration and collection of blood samples and median time (25-75th percentile) between APAP loading dose and collection of CSF were, respectively, 125 min (95-210 min) and 133 min (33-202 min). The population mean Teq, standardized to a 70-kg person, was 1.93 h (CV 43%), an estimate similar to that described in adults (2.1 h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0 mg/l to 33.0 mg/l, APAP CSF concentrations ranged from 0.0 mg/l to 21.0 mg/l.

Conclusion: Size rather than blood-brain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5 kg), 1-year-old child (10 kg), 5-year-old child (20 kg), 10-year-old child (30 kg) and adult (70 kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93 h, respectively.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Acetaminophen / blood
  • Acetaminophen / cerebrospinal fluid*
  • Adolescent
  • Age Factors
  • Analgesics, Non-Narcotic / blood
  • Analgesics, Non-Narcotic / cerebrospinal fluid*
  • Bayes Theorem
  • Body Weight
  • Brain Injuries / blood
  • Brain Injuries / cerebrospinal fluid
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male


  • Analgesics, Non-Narcotic
  • Acetaminophen