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Supramolecular Complex of Ibuprofen with Larch Polysaccharide Arabinogalactan: Studies on Bioavailability and Pharmacokinetics

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Abstract

Background and Objectives

In the present work, pharmacological and pharmacokinetic properties of the supramolecular complex of non-steroid anti-inflammatory drug ibuprofen (IBU) with natural polysaccharide arabinogalactan (AG) were studied. The main goals of such complexation were the increase of ibuprofen’s bioavailability and decrease its effective dose after oral administration.

Methods

The complex with mass ratio as IBU:AG 1:10 was obtained by mechanochemical synthesis and characterized by water solubility, electron microscopy, differential scanning calorimetry, X-ray powder diffraction analysis and 1H-nuclear magnetic resonance spectroscopy. Different animal models of pain and inflammation was used to investigate IBU:AG biological effects. Plasma concentration of IBU and its pharmacokinetic parameters were evaluated after oral introduction.

Results

It was found that ibuprofen’s effective analgesic and anti-inflammatory dose decreased twofold after its introduction as a complex with AG. The reason of this difference is due to the increase of ibuprofen concentration in rats’ plasma: C max of IBU at doses of 20 and 40 mg/kg was found as 0.088 and 0.132 μg/ml, whereas C max of IBU in the complex form was 0.103 and 0.160 μg/ml, respectively.

Conclusions

Thus, we have shown that complexation of the IBU with AG results in its bioavailability increase, reduction of the effective dose and should decrease toxic side effects.

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Authors and Affiliations

  1. Laboratory of Pharmacological Research, N.N. Vorozhtsov Institute of Organic Chemistry SB RAS, 9, Lavrentjeva Prospect, 630090, Novosibirsk, Russia

    Mikhail V. Khvostov, Sergey A. Borisov, Tatjana G. Tolstikova & Sergey V. An’kov

  2. Institute of Solid State Chemistry and Mechanochemistry SB RAS, Novosibirsk, 630090, Russia

    Alexander V. Dushkin, Biligma D. Tsyrenova & Yulia S. Chistyachenko

  3. Voevodsky Institute of Chemical Kinetics and Combustion, SB RAS, Novosibirsk, 630090, Russia

    Nikolay E. Polyakov, Galina G. Dultseva & Andrey A. Onischuk

  4. Novosibirsk State University, Novosibirsk, 630090, Russia

    Tatjana G. Tolstikova, Galina G. Dultseva & Andrey A. Onischuk

Authors
  1. Mikhail V. Khvostov
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  2. Sergey A. Borisov
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  3. Tatjana G. Tolstikova
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  4. Alexander V. Dushkin
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Corresponding author

Correspondence to Mikhail V. Khvostov.

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Funding

This publication is supported by Grants 15-04-02538 and 15-29-05792 from the Russian Foundation for Basic Research.

Conflict of interest

Mikhail V. Khvostov, Sergey A. Borisov, Tatjana G. Tolstikova, Alexander V. Dushkin, Biligma D. Tsyrenova, Yulia S. Chistyachenko, Nikolay E. Polyakov, Galina G. Dultseva, Andrey A. Onischuk, Sergey V. An’kov declare no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Approved by the Ethic Committee of the N.N. Vorozhtsov Institute of Organic Chemistry SB RAS (protocol No. 2/2015 from 21.01.2015).

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Khvostov, M.V., Borisov, S.A., Tolstikova, T.G. et al. Supramolecular Complex of Ibuprofen with Larch Polysaccharide Arabinogalactan: Studies on Bioavailability and Pharmacokinetics. Eur J Drug Metab Pharmacokinet 42, 431–440 (2017). https://doi.org/10.1007/s13318-016-0357-y

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