title: Paracetamol (acetaminophen) penetrates readily into the cerebrospinal fluid of children after intravenous administration.
abstract: BACKGROUND
  The main action of paracetamol (acetaminophen) is presumed to be in the central nervous system. The central nervous system penetration of paracetamol has been described in children with intracranial pathologies but not in children with an intact blood-brain barrier.
  
  
  OBJECTIVE
  We investigated the cerebrospinal fluid penetration of paracetamol in 32 healthy children, aged 3 months to 12 years, who were undergoing surgery in the lower body using spinal anesthesia.
  
  
  METHODS
  In this open-label prospective study, children were given a single intravenous injection of paracetamol (15 mg/kg). Cerebrospinal fluid and venous blood samples were obtained between 5 minutes and 5 hours after injection. Paracetamol concentrations were determined from the cerebrospinal fluid and plasma by using a fluorescence polarization immunoassay.
  
  
  RESULTS
  Paracetamol was detected in cerebrospinal fluid from the earliest sample at 5 minutes, although in this sample paracetamol concentration was below the limit of quantification of 1.0 mg/L. Subsequent paracetamol concentrations in cerebrospinal fluid ranged between 1.3 and 18 mg/L (median: 7.2 mg/L), plasma concentrations ranged between 2.4 and 33 mg/L, and cerebrospinal fluid/plasma ratios ranged between 0.06 and 2.0. The highest CSF paracetamol concentration was detected at 57 minutes.
  
  
  CONCLUSIONS
  Paracetamol permeates readily into the cerebrospinal fluid of children. This fast and extensive transfer enables the rapid central analgesic and antipyretic action of intravenous paracetamol.
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, Kuopio, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Kumpulainen
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
authors.forename: Toivo
authors.initials: T
authors.lastname: Halonen
authors.forename: Marja
authors.initials: M
authors.lastname: Heikkinen
authors.forename: Jouko
authors.initials: J
authors.lastname: Savolainen
authors.forename: Merja
authors.initials: M
authors.lastname: Laisalmi
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000134:cerebrospinal fluid*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000134:cerebrospinal fluid*; D000704:Analysis of Variance; D000775:Anesthesia, Spinal / Q000379:methods; D001812:Blood-Brain Barrier; D002490:Central Nervous System / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007275:Injections, Intravenous; D008297:Male; D011336:Probability; D011446:Prospective Studies; D012016:Reference Values; D013129:Spinal Puncture; D013514:Surgical Procedures, Operative / Q000379:methods; D013997:Time Factors
chemical_list: D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen