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  3. Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents)
  4. Volume 22, Issue 4
  5. Article
Volume 22, Issue 4
  • ISSN: 1871-5257
  • E-ISSN: 1875-6182

Abstract

Background

The absolute oral bioavailability of rosuvastatin (RST), a second-generation statin, is low 20% and only 10% is recovered as metabolite -desmethy l rosuvistatin. Since it is a hydrophilic statin, RST relies on the organic anion transporting polypeptide-1B1 (OATP-1B1), as the key mechanism for active transport into hepatocytes. Quercetin (QUE) being a bio enhancer and inhibitor of OATP1B1 can augment the bioavailability and pharmacokinetics of RST.

Objectives

The present study includes the development of a simple and validated bioanalytical Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) method for the estimation of RST and to study the effect of co-administration of QUE as a bio enhancer on its bioavailability.

Methods

An analytical column of Kromasil 100, C18 (250 mm × 4.6 mm, 5 μm), was used for chromatographic separationand acetonitrile (ACN): acetic acid buffer pH 3.0 adjusted with glacial acetic acid (55:45 Vol. %) as mobile phase with flow rate 1.0 ml/min monitored at 242 nm. The ACN: methanol (50:50 Vol. %) was employed as the final solvent for extraction. The developed method has been successfully applied in a study on the pharmacokinetics of the drug RST in rats after co-administration of QUE, which was carried out using non-compartmental analysis in order to estimate the blood concentration of the drug.

Results

The pharmacokinetics of RST was found to be altered significantly (highest concentration of RST in the blood () = 67.3 ng/ml to 122.2 ng/ml) ( < 0.001), area under curve (AUC) ( < 0.0001) and AUC ( = 0.0005) when co-administered with QUE at 120 min ().

Conclusion

The results are in accordance with the fact that QUE increases plasma levels in rats through herb-drug interactions.

© 2024 Bentham Science Publishers
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2024-12-01
2024-11-22

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References

  1. WHO. The World Health Organisation Report. 2021. Available From: https://apps.who.int/iris/bitstream/handle/10665/342703/9789240027053-eng.pdf
  2. OlssonA.G. McTaggartF. RazaA. Rosuvastatin: a highly effective new HMG-CoA reductase inhibitor.Cardiovasc. Drug Rev.200220430332810.1111/j.1527‑3466.2002.tb00099.x 12481202
     [Google Scholar]
  3. EndoA. The origin of the statins.Int. Congr. Ser.200412623810.1016/j.ics.2003.12.099
     [Google Scholar]
  4. AkiraE. Discovery and Development of Statins.Nat. Prod. Commun.2017128
     [Google Scholar]
  5. LennernäsH. FagerG. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors. Similarities and differences.Clin. Pharmacokinet.199732540342510.2165/00003088‑199732050‑00005 9160173
     [Google Scholar]
  6. BullanoM.F. WertzD.A. YangG.W. KamatS. BorokG.M. GandhiS. McDonoughK.L. WilleyV.J. Effect of rosuvastatin compared with other statins on lipid levels and National Cholesterol Education Program goal attainment for low-density lipoprotein cholesterol in a usual care setting.Pharmacotherapy200626446947810.1592/phco.26.4.469 16553504
     [Google Scholar]
  7. LuvaiA. MbagayaW. HallA.S. BarthJ.H. Rosuvastatin: a review of the pharmacology and clinical effectiveness in cardiovascular disease.Clin. Med. Insights Cardiol.20126CMC.S4324.10.4137/CMC.S432422442638
     [Google Scholar]
  8. MartinP.D. WarwickM.J. DaneA.L. Metabolism, excretion, and pharmacokinetics of RST in healthy adult males volunteers.Clin. Therapeut.2003252822283510.1016/S0149‑2918(03)80336‑3 14693307
     [Google Scholar]
  9. McTaggartF. Comparative pharmacology of rosuvastatin.Atheroscler. Suppl.20034191410.1016/S1567‑5688(03)00004‑7 12714032
     [Google Scholar]
  10. SimonsonS. RazaA. MartinP.D. MitchellP.D. JarchoJ.A. BrownC.D. WindassA.S. SchneckD.W. Rosuvastatin pharmacokinetics in heart transplant recipients administered an antirejection regimen including cyclosporine.Clin. Pharmacol. Ther.200476216717710.1016/j.clpt.2004.03.010 15289793
     [Google Scholar]
  11. MartinP.D. MitchellP.D. SchneckD.W. Pharmacodynamic effects and pharmacokinetics of a new HMG-CoA reductase inhibitor, rosuvastatin, after morning or evening administration in healthy volunteers.Br. J. Clin. Pharmacol.200254547247710.1046/j.1365‑2125.2002.01688.x 12445025
     [Google Scholar]
  12. BalakumarK. RaghavanC.V. selvan, N.T.; prasad, R.H.; Abdu, S. Self nanoemulsifying drug delivery system (SNEDDS) of Rosuvastatin calcium: Design, formulation, bioavailability and pharmacokinetic evaluation.Colloids Surf. B Biointerfaces201311233734310.1016/j.colsurfb.2013.08.025 24012665
     [Google Scholar]
  13. DudhipalaN. VeerabrahmaK. Improved anti-hyperlipidemic activity of Rosuvastatin Calcium via lipid nanoparticles: Pharmacokinetic and pharmacodynamic evaluation.Eur. J. Pharm. Biopharm.2017110475710.1016/j.ejpb.2016.10.022 27810472
     [Google Scholar]
  14. BegS. RazaK. KumarR. ChadhaR. KatareO.P. SinghB. Improved intestinal lymphatic drug targeting via phospholipid complex-loaded nanolipospheres of rosuvastatin calcium.RSC Advances20166108173818710.1039/C5RA24278A
     [Google Scholar]
  15. RizwanullahM. AminS. AhmadJ. Improved pharmacokinetics and antihyperlipidemic efficacy of rosuvastatin-loaded nanostructured lipid carriers.J. Drug Target.2017251587410.1080/1061186X.2016.1191080 27186665
     [Google Scholar]
  16. TatirajuD.V. BagadeV.B. KarambelkarP.J. JadhavV.M. KadamV. Natural bioenhancers: An overview.J. Pharmacogn. Phytochem.201325560
     [Google Scholar]
  17. DudhatraG.B. ModiS.K. AwaleM.M. Comprehensive review on Pharmacotherapeutics of herbal bio-enhancers.Scienti. World J20121213310.1100/2012/637953
     [Google Scholar]
  18. JavedS. AhsanW. KohliK. The concept of bio-enhancers in bioavailability enhancement of drugs–a patent review.J of Sci Letters20161143165
     [Google Scholar]
  19. WuL.X. GuoC.X. ChenW.Q. YuJ. QuQ. ChenY. TanZ.R. WangG. FanL. LiQ. ZhangW. ZhouH.H. Inhibition of the organic anion-transporting polypeptide 1B1 by quercetin: An in vitro and in vivo assessment.Br. J. Clin. Pharmacol.201273575075710.1111/j.1365‑2125.2011.04150.x 22114872
     [Google Scholar]
  20. MohosV. Fliszár-NyúlE. UngváriO. KuffaK. NeedsP.W. KroonP.A. TelbiszÁ. Özvegy-LaczkaC. PoórM. Inhibitory Effects of Quercetin and Its Main Methyl, Sulfate, and Glucuronic Acid Conjugates on Cytochrome P450 Enzymes, and on OATP, BCRP and MRP2 Transporters.Nutrients2020128230610.3390/nu12082306
     [Google Scholar]
  21. BhimanwarR. KothapalliL. KhawshiA. Quercetin as Natural Bioavailability Modulator: An Overview.Research Journal of Pharmacy and Technology20201342045205210.5958/0974‑360X.2020.00368.6
     [Google Scholar]
  22. MaalikA. KhanF.A. MumtazA. MehmoodA. AzharS. AtifM. KarimS. AltafY. TariqI. Pharmacological applications of Quercetin and its derivatives : A short review.Trop. J. Pharm. Res.2014139156110.4314/tjpr.v13i9.26
     [Google Scholar]
  23. PatelR.V. MistryB.M. ShindeS.K. SyedR. SinghV. ShinH.S. Therapeutic potential of quercetin as a cardiovascular agent.Eur. J. Med. Chem.201815588990410.1016/j.ejmech.2018.06.053 29966915
     [Google Scholar]
  24. DajasF. Abin-CarriquiryJ.A. ArredondoF. BlasinaF. EcheverryC. MartínezM. RiveraF. VaamondeL. LucíaV. Quercetin in brain diseases: Potential and limits.Neurochem. Int.20158914014810.1016/j.neuint.2015.07.002 26160469
     [Google Scholar]
  25. TatirajuV. BagadeB. KarambelkarJ. JadhavM. Kadam. Natural enhancers: An overview.J. Pharmacogn. Phytochem.201325560
     [Google Scholar]
  26. QuQ. QuJ. HanL. ZhanM. WuL. ZhangY. ZhangW. ZhouH. Inhibitory effects of phytochemicals on metabolic capabilities of CYP2D6*1 and CYP2D6*10 using cell-based models in vitro.Acta Pharmacol. Sin.201435568569610.1038/aps.2013.202 24786236
     [Google Scholar]
  27. WongC.C. AkiyamaY. AbeT. LippiatJ.D. OrfilaC. WilliamsonG. Carrier-mediated transport of quercetin conjugates: Involvement of organic anion transporters and organic anion transporting polypeptides.Biochem. Pharmacol.201284456457010.1016/j.bcp.2012.05.011 22634047
     [Google Scholar]
  28. LeeJ.H. ShinY.J. OhJ.H. LeeY.J. Pharmacokinetic interactions of clopidogrel with quercetin, telmisartan, and cyclosporine A in rats and dogs.Arch. Pharm. Res.201235101831183710.1007/s12272‑012‑1017‑7 23139136
     [Google Scholar]
  29. CermakR. WeinS. WolfframS. LangguthP. Effects of the flavonol quercetin on the bioavailability of simvastatin in pigs.Eur. J. Pharm. Sci.200938551952410.1016/j.ejps.2009.09.018 19804821
     [Google Scholar]
  30. HsiuS.L. HouY.C. WangY.H. TsaoC.W. SuS.F. ChaoP.D.L. Quercetin significantly decreased cyclosporin oral bioavailability in pigs and rats.Life Sci.200272322723510.1016/S0024‑3205(02)02235‑X 12427482
     [Google Scholar]
  31. SanaeeF. Valente NevesD. LanchoteV.L. JamaliF. Pharmacokinetics of nebivolol in the rat: Low oral absorption, loss in the gut and systemic stereoselectivity.Biopharm. Drug Dispos.201334631232010.1002/bdd.1847 23625744
     [Google Scholar]
  32. ShinS. ChoiJ. LiX. Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats.Int. J. Pharm.20063131-214414910.1016/j.ijpharm.2006.01.028 16516418
     [Google Scholar]
  33. SarikaN. YogeshP. Optimization of ex vivo permeability characteristics of berberine in presence of quercetin using 32 full factorial design.J. Appl. Pharm. Sci.201991738210.7324/JAPS.2019.90111
     [Google Scholar]
  34. ChakrabortyM. AhmedM.G. BhattacharjeeA. Effect of quercetin on myocardial potency of curcumin against ischemia reperfusion induced myocardial toxicity.Synergy20187252910.1016/j.synres.2018.09.001
     [Google Scholar]
  35. ZhaoQ. WeiJ. ZhangH. Effects of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats.Xenobiotica201949556356810.1080/00498254.2018.1478168 29768080
     [Google Scholar]
  36. JiaF.F. TanZ.R. McLeodH.L. ChenY. Ou-YangD.S. ZhouH.H. Effects of quercetin on pharmacokinetics of cefprozil in Chinese-Han male volunteers.Xenobiotica2016461089690010.3109/00498254.2015.1132792 26928207
     [Google Scholar]
  37. MaiN. PetraS. The Influence of Single-Dose and Short-Term Administration of quercetin on the Pharmacokinetics of Midazolam in Humans. J of Pharmaceu.Sci201510431993207
     [Google Scholar]
  38. SujathaS. Cidd, i V. Altered Pharmacokinetics and Pharmacodynamics of Glimepiride by the concomitant use of Quercetin in diabetic rats: PK/PD modeling.J. Pharm. Res.20159525530
     [Google Scholar]
  39. BabuP.R. BabuK.N. PeterP.L.H. RajeshK. BabuP.J. Influence of quercetin on the pharmacokinetics of ranolazine in rats and in vitro models.Drug Dev. Ind. Pharm.201339687387910.3109/03639045.2012.707209 22817837
     [Google Scholar]
  40. DiCenzoR. FrerichsV. LarppanichpoonpholP. PredkoL. ChenA. ReichmanR. MorrisM. Effect of quercetin on the plasma and intracellular concentrations of saquinavir in healthy adults.Pharmacotherapy20062691255126110.1592/phco.26.9.1255 16945047
     [Google Scholar]
  41. KimK.A. ParkP.W. KimH.K. HaJ.M. ParkJ.Y. Effect of quercetin on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in healthy subjects.J. Clin. Pharmacol.200545894194610.1177/0091270005278407 16027405
     [Google Scholar]
  42. ChoiJ.S. LiX. Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits.Int. J. Pharm.20052971-21810.1016/j.ijpharm.2004.12.004 15907592
     [Google Scholar]
  43. ChoiJ.S. HanH.K. The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits.J. Pharm. Pharmacol.201056121537154210.1211/0022357044814 15563760
     [Google Scholar]
  44. SmithN.F. FiggW.D. SparreboomA. Role of the liver-specific transporters OATP1B1 and OATP1B3 in governing drug elimination.Exp Opi on Drug Metabol & Toxi20051429245
     [Google Scholar]
  45. HoR.H. TironaR.G. LeakeB.F. GlaeserH. LeeW. LemkeC.J. WangY. KimR.B. Drug and bile acid transporters in rosuvastatin hepatic uptake: Function, expression, and pharmacogenetics.Gastroenterology200613061793180610.1053/j.gastro.2006.02.034 16697742
     [Google Scholar]
  46. MoussabaH. MahmoudstM. A validated RP-HPLC method for the determination of RST in presence of sacubitril/valsartan in rat plasma: Application to in vivo evaluation of OATP-mediated drug interaction potential between RST and sacubitril/valsartan.Microchem. J.2018143313810.1016/j.microc.2018.07.021
     [Google Scholar]
  47. VijayapandiP. Simple Method for Animal Dose Calculation in Preclinical Research.EC Pharmacol and Toxicol.202080102
     [Google Scholar]
  48. BahiaM. HanaaM. A validated RP-HPLC method for the determination of rosuvastatin in presence of sacubitril/valsartan in rat plasma: Application to in vivo evaluation of OATP-mediated drug interaction potential between rosuvastatin and sacubitril/valsartan.Microchem J.201820180122
     [Google Scholar]
/content/journals/chamc/10.2174/0118715257258735231016112348
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Evaluation of Quercetin's Bioenhancing Effect on Oral Pharmacokinetics of Rosuvastatin in Wistar Rats Using RP-HPLC Method
Cardiovasc. Hematol. Agents Med. Chem. 22, 456 (2024); https://doi.org/10.2174/0118715257258735231016112348
/content/journals/chamc/10.2174/0118715257258735231016112348
/content/journals/chamc/10.2174/0118715257258735231016112348
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  • Article Type:     Research Article
Keyword(s): bioanalytical; bioavailability; organic anion transporting system; pharmacokinetic; quercetin; RP-HPLC; RST; statins

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