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...
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Ss.Cyril and Methodius University, Skopje
2023-03-01
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Series: | Macedonian Veterinary Review |
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Online Access: | https://macvetrev.mk/LoadArticleContent?DOI=10.2478_macvetrev_2022_0031 |
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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. |
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language | English |
last_indexed | 2024-04-09T23:50:46Z |
publishDate | 2023-03-01 |
publisher | Ss.Cyril and Methodius University, Skopje |
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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 |