Acetaminophen Concentration in Cerebrospinal Fluid in Infants
Information source: Assaf-Harofeh Medical Center
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fever
Phase: N/A
Status: Completed
Sponsored by: Assaf-Harofeh Medical Center Official(s) and/or principal investigator(s):
Eran Kozer, MD, Principal Investigator, Affiliation: Assaf-Harofeh Medical Center
Summary
Acetaminophen is the most commonly used drug in children. Inhibition of COX-3 in the brain
has been suggested as the primary central mechanism by which acetaminophen decrease pain and
possibly fever. However there is very limited data about acetaminophen concentrations in the
brain and no such data is available for newborns. The objective of the current study is to
describe concentrations of acetaminophen in the fluid around the brain of infants after
administration of acetaminophen.
Clinical Details
Official title: Acetaminophen Concentration in Cerebrospinal Fluid in Infants
Study design: Prospective
Detailed description:
The mechanism by which acetaminophen causes analgesia and antipyretic effect is not entirely
clear. Recently a new COX isoenzyme was identified and termed COX 3. In humans this isoenzyme
is most abundant in cerebral cortex and heart. Inhibition of COX-3 could represent a primary
central mechanism by which acetaminophen decrease pain and possibly fever (10). An effect on
of acetaminophen on presynaptic 5-HT(2) receptors in the hypocampus has been demonstrated
(11) suggesting again that the primary effect of acetaminophen is in the CNS.
Many studies (12-16) described the pharmacokinetics of oral and rectal acetaminophen in
infants and neonates. Yet, the data on acetaminophen concentrations in the CSF is very
limited. Two studies in adults (17;18) used intravenous propacetamol and described
concentrations of acetaminophen in the plasma and CSF. Acetaminophen was detected as early as
15 minutes after the administration and reached peak concentrations in the CSF at the 4th
hour. A small study (19) of nine children who had indwelling ventricular drains found that
cerebrospinal fluid concentrations lagged behind those of plasma with an equilibration half
time of 0. 72 h. This study did not describe CSF concentrations in neonates and used a dose
of 40mg/kg, which is higher than the recommended dose in children. To the best of our
knowledge there is no data on acetaminophen CSF concentrations in neonates.
The objective of the current study is to describe concentrations of acetaminophen in the CSF
of infants after single administration of acetaminophen. A better understanding of the
pharmacokinetics of acetaminophen and its penetration into the CSF will enable us to better
predict the effects of this commonly used drug.
Eligibility
Minimum age: N/A.
Maximum age: 2 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Age: 1week - 2 years
- Rectal temperature > 38. 0OC
- A sepsis work up is indicated
- Acetaminophen was given prior to lumbar puncture (LP)
Exclusion Criteria:
- Hypersensitivity to acetaminophen
- Known metabolic disorder
- Known liver or kidney disease
- Hydrocephalus
- Informed consent could not be obtained from a legal guardian
Locations and Contacts
Pediatric Emergency Unit Assaf Harofeh Medical center, Zerifin 70300, Israel
Additional Information
Starting date: January 2004
Ending date: June 2007
Last updated: October 30, 2007
|
