Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration

The objective of this study was to examine the effect of ketoprofen with or without combination with xylazine on the level of cyclooxygenase-2 in mice. The intraperitoneal (i.p.) dose of ketoprofen and xylazine that caused an analgesic response in half of the mouse population was 1.26 mg/kg and 6.63...

Full description

Bibliographic Details
Main Authors: Khalil Abdullah Khalil, Yaareb Jaafer Mousa, Muna Hazim Alzubaidy
Format: Article
Language:English
Published: Ss.Cyril and Methodius University, Skopje 2023-03-01
Series:Macedonian Veterinary Review
Subjects:
Online Access:https://macvetrev.mk/LoadArticleContent?DOI=10.2478_macvetrev_2022_0031
_version_ 1827987680851394560
author Khalil Abdullah Khalil
Yaareb Jaafer Mousa
Muna Hazim Alzubaidy
author_facet Khalil Abdullah Khalil
Yaareb Jaafer Mousa
Muna Hazim Alzubaidy
author_sort Khalil Abdullah Khalil
collection DOAJ
description The objective of this study was to examine the effect of ketoprofen with or without combination with xylazine on the level of cyclooxygenase-2 in mice. The intraperitoneal (i.p.) dose of ketoprofen and xylazine that caused an analgesic response in half of the mouse population was 1.26 mg/kg and 6.63 mg/kg, respectively. Serum cyclooxygenase-2 concentration (activity) in the control mice was 16.94 ng/ml. The ketoprofen-treated group (2.52 mg/kg, i.p.) decreased the cyclooxygenase-2 concentration by 58% (7.16 ng/ml). The combined ketoprofen and xylazine treatment (13.26 mg/kg, i.p.) decreased the cyclooxygenase-2 by 94% (0.98 ng/ml). The ketoprofen plasma concentration in the combined treatment group was significantly higher compared to the ketoprofen treatment group. Ketoprofen plasma concentrations measured at 0.25, 0.5, 1, 2, 4, and 24 hours were 19.07, 18.94, 14.66, 6.53, 5.44, and 5.54 μg/ml, respectively. Plasma concentrations of ketoprofen and xylazine were raised to 28.74, 29.74, 15.32, 13.04, 14.64, and 11.95 μg/ml or by 51%, 56%, 5%, 100%, 169%, and 116%, respectively. Ketoprofen pharmacokinetic variables were increased (AUC0-∞ (515%), AUMC0-∞ (2389%), MRT (305%), t1/2β (375%), Tmax (100%), and Cmax (55%)), while other values were decreased (Kel (79%), Vss (25%), and Cl (88%)). Our findings suggested a synergistic interaction between ketoprofen and xylazine on the level of cyclooxygenase-2 (pharmacodynamic interaction) which was exerted by modification of the ketoprofen pharmacokinetic properties in mice.
first_indexed 2024-04-09T23:50:46Z
format Article
id doaj.art-d7ddc132d4414849810eb4fa62bce1f4
institution Directory Open Access Journal
issn 1409-7621
1857-7415
language English
last_indexed 2024-04-09T23:50:46Z
publishDate 2023-03-01
publisher Ss.Cyril and Methodius University, Skopje
record_format Article
series Macedonian Veterinary Review
spelling doaj.art-d7ddc132d4414849810eb4fa62bce1f42023-03-17T10:04:28ZengSs.Cyril and Methodius University, SkopjeMacedonian Veterinary Review1409-76211857-74152023-03-01461273310.2478/macvetrev-2022-0031Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administrationKhalil Abdullah Khalil0Yaareb Jaafer Mousa1Muna Hazim Alzubaidy2Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, IraqDepartment of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, IraqDepartment of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, IraqThe objective of this study was to examine the effect of ketoprofen with or without combination with xylazine on the level of cyclooxygenase-2 in mice. The intraperitoneal (i.p.) dose of ketoprofen and xylazine that caused an analgesic response in half of the mouse population was 1.26 mg/kg and 6.63 mg/kg, respectively. Serum cyclooxygenase-2 concentration (activity) in the control mice was 16.94 ng/ml. The ketoprofen-treated group (2.52 mg/kg, i.p.) decreased the cyclooxygenase-2 concentration by 58% (7.16 ng/ml). The combined ketoprofen and xylazine treatment (13.26 mg/kg, i.p.) decreased the cyclooxygenase-2 by 94% (0.98 ng/ml). The ketoprofen plasma concentration in the combined treatment group was significantly higher compared to the ketoprofen treatment group. Ketoprofen plasma concentrations measured at 0.25, 0.5, 1, 2, 4, and 24 hours were 19.07, 18.94, 14.66, 6.53, 5.44, and 5.54 μg/ml, respectively. Plasma concentrations of ketoprofen and xylazine were raised to 28.74, 29.74, 15.32, 13.04, 14.64, and 11.95 μg/ml or by 51%, 56%, 5%, 100%, 169%, and 116%, respectively. Ketoprofen pharmacokinetic variables were increased (AUC0-∞ (515%), AUMC0-∞ (2389%), MRT (305%), t1/2β (375%), Tmax (100%), and Cmax (55%)), while other values were decreased (Kel (79%), Vss (25%), and Cl (88%)). Our findings suggested a synergistic interaction between ketoprofen and xylazine on the level of cyclooxygenase-2 (pharmacodynamic interaction) which was exerted by modification of the ketoprofen pharmacokinetic properties in mice.https://macvetrev.mk/LoadArticleContent?DOI=10.2478_macvetrev_2022_0031cyclooxygenase-2ketoprofenmicepharmacokineticsxylazine
spellingShingle Khalil Abdullah Khalil
Yaareb Jaafer Mousa
Muna Hazim Alzubaidy
Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration
Macedonian Veterinary Review
cyclooxygenase-2
ketoprofen
mice
pharmacokinetics
xylazine
title Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration
title_full Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration
title_fullStr Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration
title_full_unstemmed Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration
title_short Pharmacokinetic criteria of ketoprofen and its cyclooxygenase-2 inhibition in mice: influence of xylazine administration
title_sort pharmacokinetic criteria of ketoprofen and its cyclooxygenase 2 inhibition in mice influence of xylazine administration
topic cyclooxygenase-2
ketoprofen
mice
pharmacokinetics
xylazine
url https://macvetrev.mk/LoadArticleContent?DOI=10.2478_macvetrev_2022_0031
work_keys_str_mv AT khalilabdullahkhalil pharmacokineticcriteriaofketoprofenanditscyclooxygenase2inhibitioninmiceinfluenceofxylazineadministration
AT yaarebjaafermousa pharmacokineticcriteriaofketoprofenanditscyclooxygenase2inhibitioninmiceinfluenceofxylazineadministration
AT munahazimalzubaidy pharmacokineticcriteriaofketoprofenanditscyclooxygenase2inhibitioninmiceinfluenceofxylazineadministration