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Published online April 2, 2007
PEDIATRICS Vol. 119 No. 4 April 2007, pp. 766-771 (doi:10.1542/peds.2006-3378)
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ARTICLE

Paracetamol (Acetaminophen) Penetrates Readily Into the Cerebrospinal Fluid of Children After Intravenous Administration

Elina Kumpulainen, BMa,b, Hannu Kokki, MD, PhDa,b, Toivo Halonen, PhDc, Marja Heikkinen, MDd, Jouko Savolainen, PhDe, Merja Laisalmi, MDb

a Departments of Pharmacology and Toxicology
e Pharmaceutical Chemistry, University of Kuopio, Kuopio, Finland
b Department of Anesthesiology and Intensive Care
c Laboratory Centre
d Department of Surgery, Kuopio University Hospital, Kuopio, Finland

INTRODUCTION. 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.

MATERIALS AND 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.

Key Words: acetaminophen • paracetamol • cerebrospinal fluid • pharmacokinetics • child • infant

Abbreviations: CNS—central nervous system • CSF— cerebrospinal fluid • PACU—postanesthesia care unit • NSAID—nonsteroidal antiinflammatory drug • BBB—blood-brain barrier

Accepted Dec 6, 2006.


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additional data on cerebrospinal fluid kinetics of paracetamol in neonates
karel allegaert
Pediatrics Online, 2 Apr 2007 [Full text]