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Clinical Drug Investigation
Published in: Clinical Drug Investigation 7/2016

01-07-2016 | Original Research Article

The Cerebrospinal Fluid Distribution of Postoperatively Administred Dexketoprofen and Etoricoxib and Their Effect on Pain and Inflammatory Markers in Patients Undergoing Hip Arthroplasty

Authors: Annika Piirainen, Merja Kokki, Heidi Hautajärvi, Marko Lehtonen, Hannu Miettinen, Kari Pulkki, Veli-Pekka Ranta, Hannu Kokki

Published in: Clinical Drug Investigation | Issue 7/2016

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Abstract

Background and Objective

Based on earlier literature, etoricoxib may have a delayed analgesic effect in postoperative setting when analgesic efficacy of nonselective nonsteroidal anti-inflammatory drug dexketoprofen is rapid. This may be caused by slow penetration of etoricoxib into the central nervous system (CNS). Therefore we decided to determine the plasma and cerebrospinal fluid (CSF) pharmacokinetics and pharmacodynamics of dexketoprofen and etoricoxib in patients with hip arthroplasty.

Methods

A total of 24 patients, scheduled for an elective primary hip arthroplasty were enrolled. After surgery, 12 subjects were randomized to received a single intravenous dose of dexketoprofen, and 12 subjects were given oral etoricoxib. Paired blood and CSF samples were taken up to 24 h for measurement of drug concentrations, interleukin (IL)-6, IL-1ra and blood for interleukin 10.

Results

In CSF the highest measured concentration (C max) of dexketoprofen was 4.0 (median) ng/mL (minimum–maximum 1.9–13.9) and time to the highest concentration (t max) 3 h (2–5), and for etoricoxib C max 73 ng/mL (36–127) and t max 5 h (1–24), respectively. Opioid consumption during the first 24 postoperative hours was similar in the two groups. Dexketoprofen and etoricoxib had a similar effect on the postoperative inflammatory response. No significant differences considering pain relief or adverse events were found between the two groups.

Conclusion

Dexketoprofen and etoricoxib entered the CNS readily, already at 30 min after administration dexketoprofen was detected in the CSF in most subjects and etoricoxib after 60 min. A single dose of dexketoprofen and etoricoxib provided a similar anti-inflammatory and analgesic response after major orthopaedic surgery.
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Metadata
Title
The Cerebrospinal Fluid Distribution of Postoperatively Administred Dexketoprofen and Etoricoxib and Their Effect on Pain and Inflammatory Markers in Patients Undergoing Hip Arthroplasty
Authors
Annika Piirainen
Merja Kokki
Heidi Hautajärvi
Marko Lehtonen
Hannu Miettinen
Kari Pulkki
Veli-Pekka Ranta
Hannu Kokki
Publication date
01-07-2016
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 7/2016
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-016-0400-4

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