Yahya, T., Mousa, Y. (2024). Pharmacodynamic and Pharmacokinetic Comparison between Selective and Non-selective COX-2 Inhibitors in Mice. Journal of Applied Veterinary Sciences, 9(2), 99-105. doi: 10.21608/javs.2024.266445.1310
Taimaa Yahya; Yaareb Jaafar Mousa. "Pharmacodynamic and Pharmacokinetic Comparison between Selective and Non-selective COX-2 Inhibitors in Mice". Journal of Applied Veterinary Sciences, 9, 2, 2024, 99-105. doi: 10.21608/javs.2024.266445.1310
Yahya, T., Mousa, Y. (2024). 'Pharmacodynamic and Pharmacokinetic Comparison between Selective and Non-selective COX-2 Inhibitors in Mice', Journal of Applied Veterinary Sciences, 9(2), pp. 99-105. doi: 10.21608/javs.2024.266445.1310
Yahya, T., Mousa, Y. Pharmacodynamic and Pharmacokinetic Comparison between Selective and Non-selective COX-2 Inhibitors in Mice. Journal of Applied Veterinary Sciences, 2024; 9(2): 99-105. doi: 10.21608/javs.2024.266445.1310
Pharmacodynamic and Pharmacokinetic Comparison between Selective and Non-selective COX-2 Inhibitors in Mice
1Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine, University of Mosul, Mosul, Iraq
2Department of Physiology, Biochemistry and Pharmacology, College of Veterinary Medicine , University of Mosul, Mosul, Iraq
Receive Date: 29 January 2024,
Revise Date: 26 February 2024,
Accept Date: 07 March 2024
Abstract
Nowadays, there is a need for good and efficacious NSAIDs with minimal side effects to be applied in veterinary medicine. The aim was to compare the pharmacodynamics (analgesia and inhibition of COX-2) and pharmacokinetics between selective (nimesulide) and non-selective (aspirin) COX-2 inhibitors in mice. Assessing the median effective doses by using the up-and-down method, COX-2 activity and plasma concentrations for both nimesulide and aspirin with their pharmacokinetic profiles in mice. The median effective doses (ED50s) of nimesulide and aspirin were found to be 7.9 and 212.23 mg/kg, respectively, using the hot-plate. Both nimesulide (15.8 mg/kg, i.m.) and aspirin (424.5 mg/kg, i.m.) inhibited COX-2 activity through a decrease in COX-2 concentrations in the plasma, liver, and kidney of mice, with superior inhibition when administering nimesulide in comparison to the control (negative and positive) and aspirin-treated groups. Plasma concentrations of nimesulide (15.8 mg/kg, i.m.) measured for different comparable periods of 0.5, 1, 2, 4, and 24 hours were higher than those of aspirin, which were 14.62, 9.22, 9.88, 7.38 and 2.27 µg/ml, respectively, while aspirin (424.5 mg/kg, i.m.) was 4.35, 3.17, 2.54, 2.25 and 1.21 µg/ml, at the same measured times. Nimesulide pharmacokinetic variables were estimated to be AUC0-∞ 169.18, AUMC0-∞ 2358,72, Kel 0.06, Cmax 14.62, Tmax 0.5, t1/2β 11.07, MRT 13.94, Vss 1.49, and Cl 0.09, while aspirin pharmacokinetic parameters differed to be 82.31, 2428.32, 0.03, 4.35, 0.5, 21.25, 158.12, and 5.16, respectively. The study concluded that nimesulide has superior pharmacological properties (analgesic, antipyretic, and anti-inflammatory) than aspirin due to its ability to inhibit COX-2 more selectively and its unique pharmacokinetics in mice, which may be useful in veterinary medicine.
ALIAS, A.S., AL-ZUBAIDY, M.H., MOUSA, Y.J., and MOHAMMAD, F.K., 2011. Plasma and whole brain cholinesterase activities in three wild bird species in Mosul, IRAQ: In vitro inhibition by insecticides. Interdisciplinary Toxicology. 4 (3): 144-148. https://doi.org/10.2478%2Fv10102-011-0022-x
Al-ZUBAIDY, M.H.I., MOUSA, Y.J., HASAN, M.M. and MOHAMMAD, F.K., 2011. Acute toxicity of veterinary and agricultural formulations of organophosphates dichlorvos and diazinon in chicks.Archives of Industrial Hygiene and Toxicology.62 (4): 317-323. https://doi.org/10.2478/10004-1254-62-2011-2139
BALAJI, T., SUBRAMANIAN, M., GNANASUNDARAM, V., RAJENDRAN, S.S., and RAJENDRAN, H.S. 2013. Nimesulide induced histopathological changes in the vas deferens of mice. Journal of Clinical and Diagnostic Research. 7 (10): 2116-2118. https://doi.org/10.7860%2FJCDR%2F2013%2F6693.3446
CAIAZZO, E., IALENTI, A., and CICALA, C., 2019. The relatively selective cyclooxygenase-2 inhibitor nimesulide: What's going on?. European Journal of Pharmacology. 848, 105-111. https://doi.org/10.1016/j.ejphar.2019.01.044
CHENG, S., XU, X., KONG, X., JIANG, Y., MO, L., LI, M., JIN, Y., HAN, Y., LI, X.L., JIN, T., and MIN, J.Z., 2022. Monitoring of salicylic acid content in human saliva and its relationship with plasma concentrations. Journal of Pharmaceutical and Biomedical Analysis. 219, 114961. https://doi.org/10.1016/j.jpba.2022.114961
DAVID, M., STUART, A.B., LAYLA, G., ALAN, T.H., RAINSFORD, K.D., and SIMONA, P., 2013. The Biotransformation and Pharmacokinetics of 14C-Nimesulide in Humans Following a Single Dose Oral Administration. Journal of Drug Metabolism and Toxicology. 4 (1): 1000140. https://doi.org/10.4172/2157-7609.1000140
GUILLE, P.G., GUILLE, P.B.E., ESPINOSA, R.L., JUAREZ-OLGUIN, H., ÁLVAREZ, G.R., BRISUELA, O.N., PORTUGAL, C.M., GARCIDUENAS, C.L., ROSALES, S.R.E., LUNA, J.M.A., MEDINA, A.R., and PACHECO, C.J.L., 2019. Pharmacokinetic variations of nimesulide in mongrel dogs according to age. Die Pharmazie. 74 (12): 728-731. https://doi.org/10.1691/ph.2019.9121
GUPTA, S.K., BANSAL, P., BHARDWAJI, R.K., and VELPANDIAN, T., 2000. Comparative anti-nociceptive, anti-inflammatory and toxicity profile of nimesulide vs nimesulide and piperine combination. Pharmacological Research. 41 (6): 657-662. https://doi.org/10.1006/phrs.1999.0640
HEMMATEENEJAD, B., JANIDINA, K., and SAEIDI-BOROUJENI, M., 2008. Spectrophotometric monitoring of nimesulide photodegradation by a combined hard-soft multivariate curve resolution-alternative least square method. Journal of Pharmaceutical and Biomedical Analysis. 47 (3): 625-630. https://doi.org/10.1016/j.jpba.2008.01.040
KANANI, K., GATOULIS, S.C., and VOELKER, M., 2015. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters. Pharmaceutics. 7 (3): 188-198. https://doi.org/10.3390/pharmaceutics7030188
KIM, J.K., CHOI, M.S., YOO, H.H., and KIM, D.H., 2022. The Intake of Coffee Increases the Absorption of Aspirin in Mice by Modifying Gut Microbiome. Pharmaceutics. 14 (4): 746. https://doi.org/10.3390/pharmaceutics14040746
KIM, M.S., PARK, Y.S., KIM, S.H., KIM, S.Y., LEE, M.H., KIM, Y.H., KIM, D.W., YANG, S.C., and KANG, J.S., 2012. Quantification of nimesulide in human plasma by high-performance liquid chromatography with ultraviolet detector (HPLC-UV): application to pharmacokinetic studies in 28 healthy Korean subjects. Journal of Chromatographic Science. 50 (5): 396-400. https://doi.org/10.1093/chromsci/bms014
KRESS, H.G., BALTOV, A., BASINASKI, A., BERGHEA, F., CASTELLSAGUE, J., CODREANU, C., COPACIU, E., GIAMBERARDINO, M.A., HAKL, M., HRAZDIRA, L., KOKAVEC, M., LEJCKO, J., NACHTNEBL, L., STANCIK, R., ŠVEC, A., TOTH, T., VLASKOVSKAl, M.V., and WORON, J., 2016. Acute pain: a multifaceted challenge - the role of nimesulide. Current Medical Research and Opinion. 32 (1): 23-36. https://doi.org/10.1185/03007995.2015.1100986
KWON, J., KIM, S., YOO, H., and LEE, E., 2019. Nimesulide-induced hepatotoxicity: A systematic review and meta-analysis. PloS one. 14 (1): e0209264. https://doi.org/10.1371/journal.pone.0209264
LI, F., CHORDIA, M.D., HUANG, T., and MACDONALD, T.L., 2009. In vitro nimesulide studies toward understanding idiosyncratic hepatotoxicity: diiminoquinone formation and conjugation. Chemical Research in Toxicology. 22 (1): 72-80. https://doi.org/10.1021/tx800152r
MOHAMMAD, F.K., MOUSA, Y.J. and HASAN, M.M., 2012. Acute toxicity and neurobehavioral effects of diphenhydramine in chicks. Journal of Poultry Science. 49 (1): 51-56. https://doi.org/10.2141/jpsa.011050
MOHAMMED, Z.T., NABI, R.Kh., MOUSA, Y.J. and MAHMOOD, M.B., 2022. Identification of Histopathological Changes Induced by Amitraz in Rats. Journal of Applied Veterinary Sciences. 7 (4): 88-93. https://doi.org/10.21608/JAVS.2022.154375.1169
MOUSA, Y.J. and MOHAMMAD, F. K., 2012. Effects of hydrogen peroxide on diazepam and xylazine sedation in chicks. Interdisciplinary Toxicology. 5 (4): 179-183. https://doi.org/10.2478/v10102-012-0030-5
MOUSA, Y. 2020. Etomidate anesthesia in chicks: Effect of xylazine. Journal of the Hellenic Veterinary Medical Society. 71 (4): 2463-2470. https://doi.org/10.12681/jhvms.25921
MOUSA, Y.J. 2021. Effect of nefopam in normal chickens and its relationship to hydrogen peroxide-induced oxidative stress. Iraqi Journal of Veterinary Sciences, 35 (Supplement I): 7-12. https://doi.org/10.33899/ijvs.2021.127013.1433
MOUSA, Y.J., AL-ZUBAIDY, M.H., and AMIN, S.M., 2021. Age-related anesthetic effect of ketamine in the chickens. Iraqi Journal of Veterinary Sciences. 35 (3): 501-506. https://doi.org/10.33899/ijvs.2020.127100.1458
MOUSA, Y.J., MAHMOOD, M.B., and MOHAMMAD, M. S., 2019. Administration of ketamine with the central and peripheral analgesics for induction of balanced anesthesia in the chicks. IOP Conference Series: Earth and Environmental Science. 388: 012021. https://doi.org/10.1088/1755-1315/388/1/012021
PALIKHE, N.S., Kim, S.H., NAM, Y.H., Ye, Y.M., and PARK, H.S., 2011. Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy, Asthma and Immunology Research. 3 (4): 273-276. https://doi.org/10.4168/aair.2011.3.4.273
PATRICK, J., DILLAHA, L., ARMAS, D., and SESSA, W.C., 2015. A randomized trial to assess the pharmacodynamics and pharmacokinetics of a single dose of an extended-release aspirin formulation. Postgraduate Medicine. 127 (6): 573–580. https://doi.org/10.1080/00325481.2015.1050341
PONG, S.F., DEMUTH, S.M., KINNEY, C.M., and DEEGAN, P., 1985. Prediction of human analgesic dosages of nonsteroidal anti-inflammatory drugs (NSAIDs) from analgesic ED50 values in mice. Archives Internationales de Pharmacodynamie et de Therapie. 273 (2): 212-220. https://pubmed.ncbi.nlm.nih.gov/3873924/
PRINESH, N.P., GANANDHAMU, S., VISHALKUMAR, S., SUDIPKUMAR, C.M., and JAINISHKUMAR, R.C., 2000. RP-HPLC Method for Determination of Several NSAIDs and Their combination. Chromatography Research International. 2013: 242868. https://doi.org/10.1155/2013/242868
PTACEK, P., MACEK, J., and KLIMA, J., 2001. Rapid and simple high-performance liquid chromatographic determination of nimesulide in human plasma. Journal of Chromatography. B, Biomedical Sciences and Applications. 758 (2): 183-188. https://doi.org/10.1016/s0378-4347(01)00180-3
RAMESH, T., RAO, P.N., and RAO, R.N., 2019. Simultaneous quantification of nimesulide, phenylpropanolamine, caffeine and chlorpheniramine in rat plasma by RP–HPLC/PDA method and application to pharmacokinetic studies in healthy rat subjects. Arabian Journal of Chemistry. 12 (8). https://doi.org/10.1016/j.arabjc.2015.01.011
RUBAK, P., HARDELI, T.F., WURTZ, M., KRISTENSEN, S.D., and HVAS, A.M., 2013. Low-dose acetylsalicylic acid therapy monitored with ultra high performance liquid chromatography. Clinical Biochemistry. 46 (12): 988-992. https://doi.org/10.1016/j.clinbiochem.2013.04.007
ZHANG, Y., HUO, M., ZHOU, J., and XIE, S., 2010. PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Computer Methods and programs in Biomedicine. 99 (3): 306-314. https://doi.org/10.1016/j.cmpb.2010.01.007