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

• Authors: Cristiana Filip , Elena Albu , Nastasia Gheorghita , Nicolae Ghitler , Georgeta Mocanu , Mihai Nechifor
• Languages of publication: EN

Abstracts

EN

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

EN

Nicotinic acid; pro-drug; plasma level; hypolipidemic effects

• Publisher: De Gruyter Open
• Journal: Open Medicine
• Year: 2006
• Volume: 1
• Issue: 4
• Pages: 348-355

Dates

published

1 - 12 - 2006

online

11 - 11 - 2006

Contributors

author

Cristiana Filip

• Department of Biochemistry, University of Medicine and Pharmacy, Iasi, Romania

author

Elena Albu

• Department of Pharmacology, University of Medicine and Pharmacy, Iasi, Romania

author

Nastasia Gheorghita

• Department of Biochemistry, University of Medicine and Pharmacy, Iasi, Romania

author

Nicolae Ghitler

• Institute of Public Health “M. Ciuca”, Iasi, Romania

author

Georgeta Mocanu

• Institute of Macromolecular Chemistry “P. Poni”, Iasi, Romania

author

Mihai Nechifor

• Department of Biochemistry, University of Medicine and Pharmacy, Iasi, Romania

References

• [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. http://dx.doi.org/10.1097/01.hco.0000231404.76930.e9[Crossref]
• [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.
• [3] The Pharmaceutical Codex, 11th ed., Pharmaceutical Press, London, 1979.
• [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. [PubMed]
• [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. http://dx.doi.org/10.1053/meta.2002.34701[Crossref]
• [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. http://dx.doi.org/10.1185/030079906X89766[Crossref]
• [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.
• [8] A.M. Gotto Jr: “Triglyceride as a risk factor for coronary artery disease”, Am. J. Cardiol., Vol. 82, (1998), pp. 22Q–25Q. [Crossref][PubMed]
• [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. http://dx.doi.org/10.1001/archinte.164.7.697[Crossref]
• [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. [PubMed][Crossref]
• [11] I. Gouni-Berthold and W. Krone: “Hypertriglyceridemia-why, when and how should it be treated?”, Z. Kardiol., Vol. 94, (2005), pp. 731–739. http://dx.doi.org/10.1007/s00392-005-0295-1[Crossref]
• [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.
• [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.
• [14] R. Gugler: “Clinical pharmacokinetics of hypolipidaemic drugs”, Clin. Pharmacokinet., Vol. 3, (1978), pp. 425–439. [PubMed][Crossref]
• [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. [Crossref]
• [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.

Identifiers

DOI

10.2478/s11536-006-0035-6