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Comparative pharmacokinetic interactions of Quercetin and Rutin in rats after oral administration of European patented formulation containing Hipphophae rhamnoides and Co-administration of Quercetin and Rutin

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Abstract

Quercetin and Rutin are most common flavone constituents of some herb extracts such as Hippophae rhamnoides L. Inter and intra herb pharmacokinetics interactions of Quercetin and Rutin were investigated in the present study. Pharmacokinetic study was investigated in the two groups of rats (n = 6) for pharmacokinetic interactions between the Quercetin and Rutin (2.5 mg/kg) mixture treated alone with European patented polyherbal formulation containing equivalent weight of the above. The total plasma concentrations of Quercetin and Rutin were determined by liquid chromatography mass spectrometry (LC–MS). A method was developed and validated according to the ICH guidelines. The results of the present study shows that there are great differences in the pharmacokinetics of Quercetin and Rutin when they are administered together and from the polyherbal formulation which will be interacted by many other constituents. The bioavailability of Quercetin was lowered from the polyherbal formulation when compared with the co-administration, whereas the Rutin bioavailability has increased from the polyherbal formulation when compared with the co-administration. The maximum plasma concentration of Quercetin from coadministration and polyherbal formulation was 165.3 ± 31.9 and 90.8 ± 21.4 ng/mL, respectively, whereas in the case of Rutin it was 61.1 ± 29.3 and 121.7 ± 19.2 ng/mL. After polyherbal formulation administration to rats the AUC0–24, AUC0–∞ and AUMC0–∞ of both Quercetin and Rutin significantly increased when compared to co-administration. The above results proved that inter and intra herb pharmacokinetic interactions between Quercetin and Rutin. Possible interactions of the other constituents with hydrolyzing enzymes in the formulation enhances the oral bioavailability of Rutin. Accordingly besides the drug herb interactions, inter and intra herb interaction might be brought into view with the wide use of herbal remedies.

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References

  • Manach C et al (1995) Quercetin metabolites in plasma of rats fed diets containing rutin or quercetin. J Nutr 125(7):1911–1922

  • Ilango K et al (2013) Emerging need of pharmacokinetics in Ayurvedic system of medicine. Int J Res Ayurveda Pharm 4(5):1–5

  • Aruna D, Naidu M (2007) Pharmacodynamic interaction studies of Gingiko biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol 63:333–338

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Brazier N, Levine M (2003) Drug-herb interaction among commonly used conventional medicines: a compendium for health care professionals. Am J Ther 10:163–169

    Article  PubMed  Google Scholar 

  • Dubey GP (2005) Herbal preparation for management of cardiovascular and neurologic disorders. European Union, Patent No. EP 1 569 666 B1

  • Erlund I et al (2000) Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Pharmacol 56:545–553

    Article  CAS  Google Scholar 

  • Formica J, Regelson W (1995) Review of the biology of Quercetin and related bioflavanoids. Food Chem Toxicol 33:1061–1080

    Article  CAS  PubMed  Google Scholar 

  • Graefe E et al (2001) Pharmacokinetics and bioavailability of quercetin glycosides in humans. J Clin Pharmacol 41:492–499

    Article  CAS  PubMed  Google Scholar 

  • Guowen L et al (2012) Pharmacokinetic properties of isorhamnetin, kaempferol and quercetin after oral gavage of total flavones of Hipphophae rhamnoides L. in rats using a UPLC-MS method. Fitoterapia 83:182–191

    Article  Google Scholar 

  • Hollman PC et al (1997) Relative bioavailability of the antioxidant flavanoids quercetin from various foods in man. FEBS Lett 418:152–156

    Article  CAS  PubMed  Google Scholar 

  • Hollman P et al (1999) The sugar moiety is a major determininant of the absorption of dietary flavanoid glycosides in man. Free Radic Res 31:569–573

    Article  CAS  PubMed  Google Scholar 

  • International Conference on Harmonization (1996) Guideline on validation of analytical procedure-methodology. IFPMA, Geneva

  • Ke L et al (2008) Intra-herb pharacokinetics interaction between quercetina nd isorhamentin. Acta Pharmacologica Sinica 29(11):1376–1382

    Article  Google Scholar 

  • Lan K, Jiang X, He J (2007) Quantitative determiniation of isorhamnetin, quercetin and kaempferol in rat plasma by liquid chromatography with electron spray ionization tandem mass spectrometry and its application to the pharmacokinetic study of isorhamnetin. Rapid Commun Mass Spectrom 21:112–120

    Article  CAS  PubMed  Google Scholar 

  • Shargel L, Susanna W-P, Andrew B (2012) Applied biopharmaceutics and pharmacokientics, 5th edn. McGraw-Hill, New York

  • Vinson JA, Jang J, Dabbagh YA, Serry MM, Cai S (1995) Plant polyphenols exhibit lipoprotein-bond antioxidant activity using an in vitro oxidation model for heart disease. J Agric Food Chem 43:2798–2799

  • Yang J et al (2012) Identificaiton of rutin deglycosylated metabolites produced by human intestinal bacteria using UPLC-Q TOF/MS. J Chromatogr B 898(1):95–100

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank the Department of Science and Technology, Government of India, for providing financial assistance to carry the work and Department of Pharmacology, SRM College of Pharmacy, SRM University, for providing facilities to carryout animal studies.

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The authors declare no conflict of interest.

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Correspondence to Ilango Kaliappan.

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Kammalla, A.K., Ramasamy, M.K., Chintala, J. et al. Comparative pharmacokinetic interactions of Quercetin and Rutin in rats after oral administration of European patented formulation containing Hipphophae rhamnoides and Co-administration of Quercetin and Rutin. Eur J Drug Metab Pharmacokinet 40, 277–284 (2015). https://doi.org/10.1007/s13318-014-0206-9

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  • DOI: https://doi.org/10.1007/s13318-014-0206-9

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