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BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access November 11, 2006

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

Cristiana Filip, Elena Albu, Nastasia Gheorghita, Nicolae Ghitler, Georgeta Mocanu and Mihai Nechifor
From the journal Open Medicine

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.

[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.e910.1097/01.hco.0000231404.76930.e9Search in Google Scholar PubMed

[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. Search in Google Scholar

[3] The Pharmaceutical Codex, 11th ed., Pharmaceutical Press, London, 1979. Search in Google Scholar

[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. Search in Google Scholar

[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.2002.3470110.1053/meta.2002.34701Search in Google Scholar PubMed

[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/10.1185/030079906X8976610.1185/030079906X89766Search in Google Scholar

[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. Search in Google Scholar

[8] A.M. Gotto Jr: “Triglyceride as a risk factor for coronary artery disease”, Am. J. Cardiol., Vol. 82, (1998), pp. 22Q–25Q. Search in Google Scholar

[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.164.7.69710.1001/archinte.164.7.697Search in Google Scholar PubMed

[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. Search in Google Scholar

[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/s00392-005-0295-110.1007/s00392-005-0295-1Search in Google Scholar PubMed

[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. Search in Google Scholar

[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. Search in Google Scholar

[14] R. Gugler: “Clinical pharmacokinetics of hypolipidaemic drugs”, Clin. Pharmacokinet., Vol. 3, (1978), pp. 425–439. Search in Google Scholar

[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. Search in Google Scholar

[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. Search in Google Scholar

Published Online: 2006-11-11
Published in Print: 2006-12-1

© 2006 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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