The impact of Cephalexin on Pharmacokinetic of Rosuvastatin In Induced Hyperlipidemia In Rabbits
DOI:
https://doi.org/10.52783/jns.v14.2843Keywords:
Hyperlipidemia, Rosuvastatin, pharmacokinetic and CephalexinAbstract
Hyperlipidemia is characterized by an abnormal blood lipid level. the most prevalent kind of dyslipidemia, hyperlipidemia (hl), it is marked by increasing levels of TG, LDL-C, and peripheral blood total cholesterol (TC), along with a decrease in HDL levels The aim of the study was to determination how Cephalexin affected on the normal microbiota that could affect Rosuvastatin pharmacokinetics in rabbits with induced hyperlipidemia. Ten rabbits were divided into two groups ware given a diet containing 1.3% cholesterol and 3% saturated fat for 40 days. and the experiment was divided into groups: G1 hyperlipidemia rabbits treated with Rosuvastatin orally 0.86 mg/kg for 7 days. G2 hyperlipidemia rabbits treated with Cephalexin ( orally) after two hours are given Rosuvastatin orally 0.86 mg/kg for 7 days. using a 3 ml plastic syringe, 1 ml of blood was drawn from each animal in each group's femoral vein, heart, jugular vein, and marginal ear vein. At 0.10, 0.30, 1, 2, 4, 6, 8, and 24 hours after treatment, the samples were taken. The amount of Rosuvastatin in the plasma was ascertained using HPLC (high-performance liquid chromatography).The results showed that co-administration of Rosuvastatin, Half-Life (T1/2): G1 has the longest half-life, while G2 have shorter half-lives. Cmax (maximum concentration): G1 shows the highest Cmax, with G2 having the lowest. Tmax (time to reach maximum concentration): G2 has the longest Tmax, indicating a delayed peak concentration compared to G1. Vd (volume of distribution): G1 has the highest Vd, suggesting a wider distribution the drug in the body. CL (clearance): G2 shows the highest clearance rate, indicating faster elimination drug. area under the curve, or AUC 0-inf: G1 has the largest AUC, indicating increased drug exposure with time. There is a significant difference between the means with different letters in the same row (P<0.05), indicating statistical differences in the pharmacokinetic parameters among the groups. In conclusion, findings provide insights into the pharmacokinetic behavior of Rosuvastatin in hyperlipidemic rabbits and suggest potential interactions when combined with antibiotics.
Downloads
Metrics
References
Al-Doseri, A. T., & Khudair, K. K. (2016). Effect of L-carnitine and/or Sitagliptin on Serum Lipids Profile of H2O2Treated Rats (Part-1). Adv Anim Vet Sci, 4(2), 71-77.
Al-Jumaili, M. A., Al-Abbass, N. N., & Ibrahim, O. M. (2024). Distribution and Elimination of the Third Generation Cephalosporins in Dogs: A Comparative Study. Diyala Journal for Veterinary Sciences, 2(3), 123-131.
Balasubramanian, R., & Maideen, N. M. (2021). HMG-CoA reductase inhibitors (statins) and their drug interactions involving CYP enzymes, P-glycoprotein and OATP transporters-an overview. Current drug metabolism, 22(5), 328-341.
Beltrán, D., Frutos-Lisón, M. D., Espín, J. C., & García-Villalba, R. (2019). Re-examining the role of the gut microbiota in the conversion of the lipid-lowering statin monacolin K (lovastatin) into its active β-hydroxy acid metabolite. Food & function, 10(4), 1787-1791.
Bera, A., Chadha, N. K., Dasgupta, S., Chakravarty, S., & Sawant, P. B. (2020). Hypoxia-mediated inhibition of cholesterol synthesis leads to disruption of nocturnal sex steroidogenesis in the gonad of koi carp, Cyprinus carpio. Fish Physiology and Biochemistry, 46(6), 2421-2435.
Caglar, S., & Toker, S. (2013). Determination of rosuvastatin at picogram level in serum by fluorimetric derivatization with 9-Anthryldiazomethane using HPLC. Journal of Chromatographic Science, 51(1), 53-58.
Chauvin, B., Drouot, S., Barrail-Tran, A., & Taburet, A. M. (2013). Drug–drug interactions between HMG-CoA reductase inhibitors (statins) and antiviral protease inhibitors. Clinical pharmacokinetics, 52(10), 815-831.
Cooper, K. J., Martin, P. D., Dane, A. L., Warwick, M. J., Raza, A., & Schneck, D. W. (2003). The effect of erythromycin on the pharmacokinetics of rosuvastatin. European journal of clinical pharmacology, 59, 51-56.
Dakheel, M. M., Al-Mnaser, S. A., Quijada, S., Woodward, M. J., & Rymer, S. (2021). Use of tannin-containing plants as antimicrobials influencing the animal health.
De Bruijn, V. M. (2024). New approach methodologies (NAMs) to understand and predict drug-induced effects on bile acid homeostasis and cholestasis (Doctoral dissertation, Wageningen University and Research).
Džidić-Krivić, A., Kusturica, J., Sher, E. K., Selak, N., Osmančević, N., Karahmet Farhat, E., & Sher, F. (2023). Effects of intestinal flora on pharmacokinetics and pharmacodynamics of drugs. Drug Metabolism Reviews, 55(1-2), 126-139.
El Nabetiti, S., Eleiwa, N. Z., Kamel, M. A., & Fahmy, A. A. (2023). Hyperlipidemia: Methods of Induction and Possible Treatments. Zagazig Veterinary Journal, 51(2), 169-184.
Firas A,Y. A., Huda, F. H. (2024). Effect Of Alpha Lipoic Acid on Pharmacokinetics of Captopril in Induced Atherosclerosis Rabbits. Afr. J. Biomed. Res 27 (2607 - 2613), 7
He, X., Zheng, N., He, J., Liu, C., Feng, J., Jia, W., & Li, H. (2017). Gut microbiota modulation attenuated the hypolipidemic effect of simvastatin in high-fat/cholesterol-diet fed mice. Journal of proteome research, 16(5), 1900-1910.
Herman, T. F., & Hashmi, M. F. (2023). Cephalexin. In StatPearls [Internet]. StatPearls Publishing.
Ibrahim, O. M. S., Sarhan, S. R., & Salih, S. I. (2016). Activity of isolated staphylococcal bacteriophage in treatment of experimentally induced chronic osteomyelitis in rabbits. Adv. Anim. Vet. Sci, 4(11), 593-603.
Jadaan, G. H., & Khudair, K. K. (2023). Curcumin phytosome as an anti-inflammatory and hypolipidemic in nano-silicon treated female rats. Adv. Anim. Vet. Sci, 11(12), 2023-2029.
Jang, D., Jung, Y. S., Kim, M. S., Oh, S. E., Nam, T. G., & Kim, D. O. (2019). Developing and validating a method for separating flavonoid isomers in common buckwheat sprouts using HPLC-PDA. Foods, 8(11), 549.
Jourova, L., Anzenbacher, P., & Anzenbacherova, E. (2016). Human gut microbiota plays a role in the metabolism of drugs. Biomedical Papers of the Medical Faculty of Palacky University in Olomouc, 160(3).
Kafi, L. A. (2014). A comparative study between olive oil and Nigella Sativa oil in treatment of hyperlipidemia induced in male albino mice. The Iraqi Journal of Veterinary Medicine, 38(2), 123-127.
Kbyeh, F. R., & Abedsalih, A. N. (2023). Antibacterial effect of co-administration of diclofenac and ciprofloxacin against infection induced by resistance e coli (o157-h7) in female rabbits Adv. Anim. Vet. Sci, 11(10), 1628-1638.
Kim, D. H. (2015). Gut microbiota-mediated drug-antibiotic interactions. Drug Metabolism and Disposition, 43(10), 1581-1589.
Mak, W. Y., Tan, S. S., Wong, J. W., Chin, S. K., & Lim, A. B. (2016). Pharmacokinetic Comparison and Bioequivalence Study of Two Rosuvastatin 20 mg Formulations in Healthy Volunteers. J Bioequiv Availab, 8, 095-098.
McTaggart, F. (2003). Comparative pharmacology of rosuvastatin. Atherosclerosis Supplements, 4(1), 9-14.
Mescher AL (2010). Junqueira, s basic histology text and atlas.12th Ed: 1-5.
Mu, C., & Zhu, W. (2019). Antibiotic effects on gut microbiota, metabolism, and beyond. Applied microbiology and biotechnology, 103(23), 9277-9285.
Onwe, P., Folawiyo, M., Anyigor-Ogah, C. S., Umahi, G., Okorocha, A. E., & Afoke, A. (2015). Hyperlipidemia: etiology and possible control. IOSR J Dent Med Sci, 14(10), 93-100.
Pehlivanović, B., Čaklovica, K., Lagumdžija, D., Žiga Smajić, N., & Bečić, F. (2021). In-vitro evaluation of pleiotropic properties of rosuvastatin. Int. J. Pharm. Sci. Res, 12(2), 1000-6.
Rozha, S. O., Hawraz, F. M., Harseen, M. R., Hassan, A. H., Rebin, K. M., Dyary, H. O., ... & Soz, M. M. (2021). Green walnut husk ameliorating the adverse effects induced by high fat diet in rats. The Iraqi Journal of Veterinary Medicine, 45(2), 60-68.
Shediwah, F. M. H., Naji, K. M., Gumaih, H. S., Alhadi, F. A., Al-Hammami, A. L., & D'Souza, M. R. (2019). Antioxidant and antihyperlipidemic activity of Costus speciosus against atherogenic diet-induced hyperlipidemia in rabbits. Journal of integrative medicine, 17(3), 181-191.
Stone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., ... & Wilson, P. W. (2014). 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, 63(25 Part B), 2889-2934.
Sulaiman, R. R., Marif, H. F., Ali, B. A., Ali, K. N., & Shekh, M. O. B. (2024). Genetic Variability and Antibacterial Sensitivity of Dichelobacter nodosus and Fusobacterium necrophorum Infection in Sheep Sulaimani Province, Kurdistan Region, Iraq. The Iraqi Journal of Veterinary Medicine, 48(1), 93-100.
Taher, M. A., Abdul-Hussain, D. A., Hasan, H. F., Fahmi, Z. M., Luaibi, O. K., & Ali, M. G. (2015). Hypolipidemic effect of caffeic acid isolated from Arctium lappa cultivated in Iraq, in hyperlipidemic rat model. Iraqi Journal of Pharmaceutical Sciences, 24(1), 18-24.
Vieira-Silva, S., Falony, G., Belda, E., Nielsen, T., Aron-Wisnewsky, J., Chakaroun, R., ... & Raes, J. (2020). Statin therapy is associated with lower prevalence of gut microbiota dysbiosis. Nature, 581(7808), 310-315.
Wilmanski, T., Kornilov, S. A., Diener, C., Conomos, M. P., Lovejoy, J. C., Sebastiani, P., ... & Gibbons, S. M. (2022). Heterogeneity in statin responses explained by variation in the human gut microbiome. Med, 3(6), 388-405.
Yao, Y. S., Li, T. D., & Zeng, Z. H. (2020). Mechanisms underlying direct actions of hyperlipidemia on myocardium: an updated review. Lipids in Health and Disease, 19(1), 1-6.
Yoo, D. H., Kim, I. S., Van Le, T. K., Jung, I. H., Yoo, H. H., & Kim, D. H. (2014). Gut microbiota-mediated drug interactions between lovastatin and antibiotics. Drug Metabolism and Disposition, 42(9), 1508-1513.
Zhang, X., Han, Y., Huang, W., Jin, M., & Gao, Z. (2021). The influence of the gut microbiota on the bioavailability of oral drugs. Acta Pharmaceutica Sinica B, 11(7), 1789-1812.
Zimmermann, F., Roessler, J., Schmidt, D., Jasina, A., Schumann, P., Gast, M., ... & Haghikia, A. (2020). Impact of the gut microbiota on atorvastatin mediated effects on blood lipids. Journal of Clinical Medicine, 9(5), 1596.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
