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Diffusion of ketoprofen into the cerebrospinal fluid of young children
Hannu Kokki1, Marko Karvinen, Antti Jekunen
1Department of Anaesthesiology and Intensive Care, Kuopio University Hospital, Kuopio, Finland. hannu.kokki@kuh.fi
Insights
Ketoprofen did not reach measurable levels in cerebrospinal fluid (CSF) in children after a single oral dose. Even with high plasma concentrations, CSF levels remained undetectable, suggesting the dose was too low for therapeutic effect in the central nervous system.
Area of Science:
- Pharmacokinetics
- Pediatric Pharmacology
- Neuroscience
Background:
- Investigating ketoprofen's entry into the cerebrospinal fluid (CSF) after oral administration.
- Determining the minimum plasma concentration required for detectable CSF levels.
Purpose of the Study:
- To assess ketoprofen's penetration into the CSF following a single oral dose of 1 mg/kg in children.
- To establish the lowest plasma ketoprofen concentration yielding measurable CSF levels.
Main Methods:
- 10 healthy children (9-86 months) post-spinal anesthesia received a single oral dose of ketoprofen syrup (1 mg/kg).
- CSF and plasma samples were collected 30 minutes post-administration.
- Ketoprofen concentrations were quantified using validated high-performance liquid chromatography (HPLC) with a 0.02 µg/mL lower limit of detection.
Main Results:
- Ketoprofen was detectable in CSF in only one child with the highest plasma concentration (7.4 µg/mL).
- At plasma concentrations of 6.5 µg/mL or lower, CSF ketoprofen levels were unmeasurable.
- The observed CSF/plasma ratio was 0.008.
Conclusions:
- A single oral dose of 1 mg/kg ketoprofen is insufficient to achieve measurable CSF levels within 30 minutes in pediatric patients.
- The findings suggest limitations in ketoprofen's central nervous system penetration at this dosage.
Background:
The objective was to examine whether or not ketoprofen enters the cerebrospinal fluid after a single oral dose of 1 mg.kg-1 syrup, and to find out what is the lowest plasma concentration that will achieve a measurable level in the cerebrospinal fluid.
Methods:
We measured ketoprofen concentrations both in plasma and cerebrospinal fluid of 10 young and healthy children (aged 9-86 months) after surgery with spinal anaesthesia. Samples of cerebrospinal fluid were collected 30 min after drug administration, at the same time as venous blood samples. A validated high-performance liquid chromatography method with a lower limit of 0.02 microg x ml(-1) was used to detect ketoprofen concentrations in cerebrospinal fluid and plasma.
Results:
Ketoprofen was detectable in the cerebrospinal fluid only in the child who had the highest plasma concentration, 7.4 microg x ml(-1), while at plasma concentrations 6.5 microg x ml(-1) or less, cerebrospinal fluid (CSF) concentrations remained unmeasurable. The detected CSF/plasma ratio was 0.008.
Conclusions:
These results indicate that ketoprofen at a dose of 1 mg x kg(-1) is too low to produce measurable CSF levels within 30 min of oral administration.
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