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Pharmaceutical Chemistry Journal

, Volume 50, Issue 5, pp 323–327 | Cite as

Preclinical Pharmacokinetic and Pharmacodynamic Studies of Pharmaceutical Compositions of the Dipeptide Anxiolytic GB-115

  • V. P. Zherdev
  • S. S. Boiko
  • M. A. Konstantinopol’skii
  • S. Yu. Raskin
  • K. V. Alekseev
  • T. A. Gudasheva
  • V. A. Mart’yanov
  • L. G. Kolik
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Four pharmaceutical compositions for oral use that contained the dipeptide anxiolytic GB-115 as the active ingredient underwent preclinical trials in male laboratory white rats. Various excipients added to the compositions and their preparation technologies had significant effects on the dipeptide pharmacokinetics. It was shown that compositions 2 and 4 had advantages according to the main pharmacokinetic characteristics reflecting the bioavailability of GB-115. The pharmacological activities of GB-115 compositions 1 – 4 at oral doses of 0.3 – 0.9 mg/kg were studied in an elevated plus-maze (EPM) test. It was established that composition 4, which included micronized substance and a hydrophilic matrix with controlled release of the active ingredient (hydroxypropylmethylcellulose), possessed the highest anxiolytic activity and increased the residence time in the EPM open arms at doses of 0.3 mg/kg (p < 0.01) and 0.9 mg/kg (p < 0.01) as compared with the placebo group. Pharmaceutical composition 4 could be recommended for creating a controlled-release solid dosage form based on the comprehensive studies.

Keywords

pharmacokinetics anxiety dipeptide GB-115 micronization hydroxypropylmethylcellulose rats 

References

  1. 1.
    X. H. Zhou and A. L. W. Po, Int. J. Pharm., 75, 97 – 115 (1991).CrossRefGoogle Scholar
  2. 2.
    E. V. Ivannikova, V. P. Zherdev, S. S. Boiko, et al., Farmakokinet. Farmakodin., No. 2, 1 – 17 (2013).Google Scholar
  3. 3.
    T. A. Gudasheva, V. P. Lezina, E. P. Kir’yanova, et al., Bioorg. Khim., 39(3), 293 – 302 (2013).PubMedGoogle Scholar
  4. 4.
    L. G. Kolik, M. A. Konstantinopol’skii, I. V. Rybina, et al., Byull. Eksp. Biol. Med., 155(2), 163 – 166 (2013).CrossRefGoogle Scholar
  5. 5.
    L. G. Kolik, I. A. Kadnikov, V. N. Zhukov, et al., Eksp. Klin. Farmakol., 74(10), 52 – 56 (2010).Google Scholar
  6. 6.
    K. V. Alekseev, N. V. Tikhonova, E. V. Blynskaya, et al., Vestn. Nov. Med. Tekhnol., 19(4), 43 – 47 (2012).Google Scholar
  7. 7.
    S. S. Boiko, G. B. Kolyvanov, V. P. Zherdev, et al., Byull. Eksp. Biol. Med., 144(9), 285 – 287 (2007).Google Scholar
  8. 8.
    A. A. Agafonov and V. K. Piotrovskii, Khim.-farm. Zh., 18(7), 845 – 849 (1984).Google Scholar
  9. 9.
    S. Pellow and S. File, J. Neurosci. Methods, 14, 149 – 167 (1985).Google Scholar
  10. 10.
    K. G. Turchinskaya, Author’s Abstract of a Candidate Dissertation in Pharmaceutical Sciences, Moscow (2015).Google Scholar
  11. 11.
    D. Q. M. Craig, Int. J. Pharm., 231, 131 – 144 (2002).CrossRefPubMedGoogle Scholar
  12. 12.
    R. Tiwari, G. Tiwari, B. Srivastava, et al., Int. J. PharmTech. Res., 4(1), 1338 – 1349 (2009).Google Scholar
  13. 13.
    R. U. Khabriev, V. Yu. Reshetnyak, V. A. Popkov, et al., Khim.-farm. Zh., 43(11), 25 – 29 (2009); Pharm. Chem. J., 43(11), 625 – 631 (2009).Google Scholar
  14. 14.
    C. L. Li, L. G. Martini, G. L. Ford, et al., J. Pharm. Pharmacol., 57(5), 533 – 546 (2005).CrossRefPubMedGoogle Scholar
  15. 15.
    S. A. Mitchell and K. M. Balwinski, J. Pharm. Sci., 97(6), 2277 – 2285 (2008).Google Scholar
  16. 16.
    J. B. Park, J. Lim, C. Y. Kang, et al., Curr. Drug Delivery, 10(6), 732 – 741 (2013).CrossRefGoogle Scholar
  17. 17.
    N. Todoran, A. Ciurba, S. A. Hussein, et al., Rev. Med. Chir. Soc. Med. Nat., Iasi, 118(4), 1143 – 1149 (2014).Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • V. P. Zherdev
    • 1
  • S. S. Boiko
    • 1
  • M. A. Konstantinopol’skii
    • 1
  • S. Yu. Raskin
    • 1
  • K. V. Alekseev
    • 1
  • T. A. Gudasheva
    • 1
  • V. A. Mart’yanov
    • 1
  • L. G. Kolik
    • 1
  1. 1.Zakusov State Institute of PharmacologyRussian Academy of Medical SciencesMoscowRussia

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