Advertisement

Central European Journal of Medicine

, Volume 1, Issue 4, pp 348–355 | Cite as

Hypolipidemic effect of a pro-drug containing nicotinic acid in rats

  • Cristiana Filip
  • Elena Albu
  • Nastasia Gheorghita
  • Nicolae Ghitler
  • Georgeta Mocanu
  • Mihai Nechifor
Research Article

Abstract

We studied the release of nicotinic acid from a macromolecular pro-drug containing niacin bound to a polymeric support of dextran. Using a modified High-performance Liquid Chromatography (HPLC) method to provide an improved separation between nicotinic acid and its metabolites, we compared the plasma levels of nicotinic acid 24 h after administration of the pro-drug or a similar dose of unbound nicotinic acid to rats. Nicotinic acid exerts a number of pharmacological activities among which is the hypolipidemic effect. To determine the hypolipidemic effect of the pro-drug, we measured the triglyceride levels and examined the correlation with the plasma levels of nicotinic acid.Starting 6 h after administration of the pro-drug, the plasma levels of nicotinic acid were high enough to cause a decrease in the triglyceride level. These results suggest that nicotinic acid was gradually released from the polymeric support, leading to the sustained presence of the active substance and, therefore, a reduction in the level of triglycerides.

Keywords

Nicotinic acid pro-drug plasma level hypolipidemic effects 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    L.A. Carlson: “Nicotinic acid and other therapies for raising high-density lipoprotein Nicotinic acid”, Curr. Opin. Cardiol., Vol. 21, (2006), pp. 336–344.PubMedCrossRefGoogle Scholar
  2. [2]
    Y. Lomnicky, M. Friedman, M.H. Luria, I. Raz and A. Hoffman: “The effect of the mode of administration on the hypolipidaemic activity of niacin: continuous gastrointestinal administration of low-dose niacin improves lipid-lowering efficacy in experimentally-induced hyperlipidaemic rats”, J. Pharm. Pharmacol., Vol. 50, (1988), pp. 1233–1239.Google Scholar
  3. [3]
    The Pharmaceutical Codex, 11th ed., Pharmaceutical Press, London, 1979.Google Scholar
  4. [4]
    N. Hengen, V. Seiberth and M. Hengen: “High-performance liquid-chromatoghaphic determination of free nicotinic acid and its metabolite, nicotinuric acid, in plasma and urine”, Clin. Chem., Vol. 24, (1978), pp. 1740–1743.PubMedGoogle Scholar
  5. [5]
    J. Pan, J.T. Van, E. Chan, R.L. Kesala, M. Lin and M.A. Charles: “Extended-release niacin treatment of the atherogenic lipid profile and lipoprotein(a) in diabetes”, Metabolism, Vol. 51, (2002), pp. 1120–1127.PubMedCrossRefGoogle Scholar
  6. [6]
    A. Vogt, U. Kassner, U. Hostalek, E. Steinhagen-Thiessen; NAUTILUS Study Group: “Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study”, Curr. Med. Res. Opin., Vol. 22, (2006), pp. 417–425.PubMedCrossRefGoogle Scholar
  7. [7]
    G. Mocanu, A. Airinei, and A. Carpov: “Macromolecular drug-conjugates. IV Nicotinic acid and nicotinamide/dextran derivatives”, STP Pharma. Sci., Vol. 4, (1994), pp. 287–291.Google Scholar
  8. [8]
    A.M. Gotto Jr: “Triglyceride as a risk factor for coronary artery disease”, Am. J. Cardiol., Vol. 82, (1998), pp. 22Q–25Q.PubMedGoogle Scholar
  9. [9]
    J. McKenney:” New perspectives on the use of niacin in the treatment of lipid disorders”, Arch. Intern. Med., Vol. 164, (2004), pp. 697–705.PubMedCrossRefGoogle Scholar
  10. [10]
    H.N. Ginsberg: “Identification and treatment of hypertriglyceridemia as a risk factor for coronary heart disease”, Curr. Cardiol. Rep., 1999, Vol. 1, (1999), pp. 233–237.Google Scholar
  11. [11]
    I. Gouni-Berthold and W. Krone: “Hypertriglyceridemia-why, when and how should it be treated?”, Z. Kardiol., Vol. 94, (2005), pp. 731–739.PubMedCrossRefGoogle Scholar
  12. [12]
    K. Takikawa, K. Miyazaki and T. Arita: “High-performance liquid chromatographic determination of nicotinic acid and its metabolites, nicotinuric acid and nicotinamide, in plasma”, J. Chromatogr., Vol. 233, (1982), pp. 343–348.PubMedGoogle Scholar
  13. [13]
    L. Saubetin, G. Galli, L. Puglisi, M.G. Ciapponi and R. Paoletti: “Analysis of free nicotinic acid released by a polymeric preparation using a mass fragmentographic technique”, Pharmacol. Res. Commun., Vol. 2, (1981), pp. 141–149.Google Scholar
  14. [14]
    R. Gugler: “Clinical pharmacokinetics of hypolipidaemic drugs”, Clin. Pharmacokinet., Vol. 3, (1978), pp. 425–439.PubMedGoogle Scholar
  15. [15]
    K. Shibata: “Simultaneous Measurement of nicotinic acid and its major metabolite in blood and urine by a reversed-phase high-performance liquid chromatography”, Agric. Biol. Chem., Vol. 52, (1988), pp. 2973–2976.Google Scholar
  16. [16]
    M. Iwaki, T. Ogiso, H. Hayashi, E.T. Lin and L.Z. Benet: “Simultaneous measurement of nicotinic acid and its major metabolite, nicotinuric acid in urine using high-performance liquid chromatography; application of solid-liquid extraction”, J. Chromatogr., Vol. 661, (1994), pp. 154–158.Google Scholar

Copyright information

© Versita Warsaw and Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Cristiana Filip
    • 1
  • Elena Albu
    • 4
  • Nastasia Gheorghita
    • 1
  • Nicolae Ghitler
    • 2
  • Georgeta Mocanu
    • 3
  • Mihai Nechifor
    • 1
  1. 1.Department of BiochemistryUniversity of Medicine and PharmacyIasiRomania
  2. 2.Institute of Public Health “M. Ciuca”IasiRomania
  3. 3.Institute of Macromolecular Chemistry “P. Poni”IasiRomania
  4. 4.Department of PharmacologyUniversity of Medicine and PharmacyIasiRomania

Personalised recommendations