Effects of D-003, a new hypocholesterolaemic and antiplatelet compound, on lipid profile and lipid peroxidation in healthy volunteers

Clinical Drug Investigation

Volumn 23, Issue 3, 2003, Pages 193-203

  Castaño, Gladys ^a   Menéndez, Roberto ^b   Más, Rosa ^b   Ledón, Nuris ^b   Fernández, Julio ^b   Pérez, Johany ^b   González, Rosa M ^b   Lezcay, Magnolia ^a  

^a Medical Surgical Research Center   (Cuba)

^b NATL CENTER FOR SCIENTIFIC RESEARCH   (Cuba)

Author keywords

[No Author keywords available]

Indexed keywords

ANTITHROMBOCYTIC AGENT; D 003; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYPOCHOLESTEROLEMIC AGENT; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PLACEBO; TRIACYLGLYCEROL; UNCLASSIFIED DRUG;

ADULT; ARTICLE; ATHEROGENESIS; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DRUG EFFECT; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; GASTRITIS; HUMAN; LIPID PEROXIDATION; MALE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REPRODUCIBILITY;

EID: 0037236311     PISSN: 11732563     EISSN: None     Source Type: Journal    
DOI: 10.2165/00044011-200323030-00005     Document Type: Article

References (54)

1. Falk E, Fernández-Ortiz A. Role of thrombosis in atherosclerosis and its complications. Am J Cardiol 1995; 75: 1B-7B
2. Murray CJL, López AD. Alternate projections of mortality and disability by cause 1990-2020. Global Burden disease Study. Lancet 1997; 349: 1498-504
3. Brown MS, Goldstein JL. Heart attacks: gone with the century. Science 1996; 272: 629-30
4. Frick MH, Elo O, Happa K, et al. Helsinki Heart Study: primary-prevention with gemfibrozil in middle-aged men with dyslipidemia. N Engl J Med 1987; 317: 1237-45
5. Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results: I. reduction in the incidence of coronary heart disease. JAMA 1984; 251: 351-64
6. Lipid Research Clinics Program. The lipid research clinics coronary primary prevention trial results: II. the relationship of reduction in the incidence of coronary heart disease to cholesterol-lowering. JAMA 1984; 251: 365-44
7. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383-9
8. Sacks FM, Pfeffer MA. , Moyé LA, et al., for the Cholesterol and Recurrent Events Trial Investigators: The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996; 335: 1001-9
9. The Long-Term Intervention with Paravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and deaths with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998; 339: 1349-57
10. Shepherd S, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995; 333: 1301-7
11. Downs JR, Clearfield M, Weiss S, et al. , for the AFCAPS/TexCAPS Research Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. JAMA 1998; 279: 1615-22
12. Wheeler D. Are there potential non lipid-lowering uses of statins? Drugs 1998; 56: 517-22
13. Davignon J. The pleiotropic effects of drugs affecting lipid metabolism. In: Atherosclerosis. Proceedings of the XIth International Symposium on Atherosclerosis; Elsevier 1997, 63-77
14. Palomäki A, Malminiemi K, Malminiemi O, et al. Effects of lovastatin therapy on susceptibility of LDL to oxidation during α-tocopherol supplementation. Arterioscler Thromb Vasc Biol 1999; 19: 1541-8
15. Aviram M, Dankner G, Cogan U, et al. Lovastatin inhibits low-density lipoprotein oxidation and alters its fluidity and uptake by macrophages: in vitro and in vivo studies. Metabolism 1992; 41: 229-35
16. Chen L, Haught WH, Yang B, et al. Preservation of endogenous antioxidant activity and inhibition of lipid peroxidation as a common mechanism of antiatherogenic effects of vitamin E, lovastatin and amlodipine. J Am Coll Cardiol 1997; 30: 569-75
17. Hussein O, Schlezinger S, Rosenbest M, et al. Reduced susceptibility of low density lipoprotein (LDL) to lipid peroxidation after fluvastatin therapy no associated with the hypocholesterolemic effect of the drug and its binding to the LDL. Atherosclerosis 1997; 128: 11-8
18. Leonhardt W, Kurktschen T, Meissner D, et al. Effects of pravastatin therapy on lipids, antioxidants, oxidations of low density lipoproteins and trace metals. Eur J Clin Pharmacol 1992; 53: 65-9
19. González L, Marrero D, Laguna A, et al., inventors. Laboratorios Dalmer SA, assignee. Mixture of primary fatty acids of high molecular weight obtained from sugar cane wax and its pharmaceutical uses. Republic of South Africa patent 98-2744. 1998 Dec 30
20. Gámez R, Mendoza S, Man R. et al. Dose-dependent cholesterol-lowering effects of D-003 on normocholesterolemic rabbits. Curr Ther Res Clin Exp 2000; 61: 8-16
21. Mendoza S, Gámez R, Noa M, et al. The effects of D-003 and policosanol on the lipid profile and endothelemia cells in normocholesterolemic rabbits: a head to head comparison. Curr Ther Res 2001: 62: 209-20
22. Menéndez R, Más R, Amor AM, et al. Inhibition of cholesterol biosynthesis in cultured fibroblasts by D-003, a mixture of very long chain saturated fatty acids. Pharmacol Res 2001; 44: 299-304
23. Castaño G, Mas R, Fernández L, et al. Assessment of the effects of D-003, a new antiplatelet and lipid-lowering compound, in healthy volunteers. Drugs R&D 2002; 3: 333-48
24. Mas R. Policosanol. Drugs of the Future 2000; 25: 569-86
25. Hernández F, Illnait J, Más R, et al. Effects of policosanol on serum lipids and lipoproteins in healthy volunteers. Curr Ther Res 1992: 51: 568-75
26. Más R, Castaño G, Illnait J, et al. Effect of policosanot in patients with type II hypercholesterolemia and additional coronary risk factors. Clin Pharmacol Ther 1998; 65: 439-47
27. Castaño G, Más R, Arruzazabala ML, et al. Effects of policosanol, pravastatin on lipid profile, platelet aggregation, endothelemia in older hypercholesterolemic patients. Int J Clin Pharm Res 1999; 19: 105-16
28. Fernández JC, Más R, Castaño G, et al. Comparison of the efficacy, safety and tolerabitity of policosanol versus fluvastatin in elderly hypercholesterolemic women. Clin Invest 2001; 21: 103-13
29. Mirkin A, Mas R, Martinto M, et al. Efficacy and tolerability of policosanol in hypercholesterolemic postmenopausal women. Int J Clin Pharmacol Res 2001; 21: 31-42
30. Crespo N, Illnait J, Más R, et al. Comparative study of the efficacy and toterability of policosanol and lovastatin in patients with hypercholesterolemia and non insulin dependent diabetes mellitus. Int J Clin Pharm Res 1999; 19 (4): 117-27
31. Fraga V, Menéndez R, Amor AM, et al. Effect of policosanol on in vitro and in vivo rat liver microsomal lipid peroxidation. Arch Med Res 1997; 28: 355-60
32. Menéndez R, Más R, Amor AM, et al. Effects of policosanol treatment on the susceptibility of low density lipoprotein (LDL) isolated from healthy volunteers to oxidative modification in vitro. Br J Clin Pharmacol 2000; 50: 255-62
33. Menéndez R, Más R, Amor AM, et al. Effects of policosanol on the susceptibility of low-density lipoprotein isolated from hypercholesterolemic patients at high coronary risk to in vitro copper-mediated lipid peroxidation: a randomized double-bind pilot study. Curr Ther Res 2000; 61: 609-20
34. Menéndez R, Mas R, Pérez Y, et al. Inhibition of rat lipoprotein lipid peroxidation by the oral administration of D-003, a mixture of very long chain saturated fatty a. Can J Physiol Pharmacol 2002; 80: 13-21
35. Mackness MI, Durington PN. HDL, its enzymes and its potential to influence lipid peroxidation. Atherosclerosis 1995; 115: 243-53
36. Watson AD, Berliner AJ, Hama SY, et al. Protective effect of high-density lipoprotein associated paraoxonase. J Clin Invest 1995; 96: 1882-91
37. Gámez R, Más R, Noa M, et al. Acute and subchronic oral toxicity of D-003 in rats. Toxicol Lett 2000; 118: 31-41
38. Gámez R, González JE, Rodeiro I, et al. In vivo genotoxic evaluation of D-003, a mixture of very long-chain aliphatic acids. J Med Food 2001; 4: 85-92
39. Gámez R, Rodeiro I, Fernández I, Acosta PC. A preliminary evaluation of the cytotoxic and genotoxic potential of D-003: a mixture of very long chain fatty acids. Teratog Carcinog Mutagen 2001; 21: 85-92
40. Schectman G, Hiatt J. Drug therapy for hypercholesterolemia in patients with cardiovascular disease: factors limiting achievement of lipid goals. Am J Med 1996; 100: 197-204
41. Seigler L, Wu WT. Separation of serum high-density lipoprotein for cholesterol determination: ultracentrifugation vs precipitation with sodium phospbotungstat and magnesium chloride. Clin Chem 1981; 27: 838-41
42. Friedewald WT, Levy RI. Friederickson SD. Estimation of the concentration of low-density-lipoprotein cholesterol in plasma without of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
43. Kleinveld HA, Hark-Lemmers HLM, Stalenhoef AFH, et al. Improved measurements of low-density lipoprotein susceptibility to copper-induced oxidation: application of a short procedure for isolating low-density lipoprotein. Clin Chem 1992; 38: 2066-72
44. Esterbauer H, Striegl H, Puhl H, et al. Continuos monitoring of in vitro oxidation of human low density lipoprotein. Free Radic Res Commun 1989; 6: 67-75
45. Markwell MA, Hass SM, Bieber LL, et al. A modification of the Lowry procedure to simply protein determination in membrane and lipoprotein samples. Anal Biochem 1987; 87: 206-10
46. Steinbrecher UP. Oxidation of human low-density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxides. J Biol Chem 1987; 262: 3603-8
47. Witztum JL. Steinberg D. Role of oxidized low-density lipoprotein in atherogenesis. J Clin Invest 1991; 88: 1785-92
48. Endemann G, Stamon LW, Madden KS, et al. CD 36 is a receptor for oxidized low-density lipoprotein. J Biol Chem 1993; 268: 11811-4
49. Brown MS, Goldstein JL. Scavenging for receptors. Nature (London) 1990; 342: 508-9
50. Ruiz J, Blanche H, James RW, et al. The role of lipid peroxidation and antioxidants in oxidative modification of LDL. Free Radic Biol Med 1992; 13: 341-6
51. Keichl S, Aichner F, Gerstenbrand F. Body iron stores and presence of carotid atherosclerosis: results from the Bruneck study. Arterioscler Thromb 1994; 14: 1625-30
52. Esterbauer H, Gebicki J, Puhl H, et al. The role of lipid peroxidation and antioxidant in oxidative modification of LDL. Free Radic Biol Med 1992; 13: 341-90
53. Thomas CE, Jackson RL. Lipid hydroperoxides involvement in copper-dependent and independent lipid peroxidation of LDL. J Pharm Exp Ther 1991; 256: 1182-8
54. O'Leary VJ, Darley-Usmar VM, Rusell LJ, et al. Pro-oxidant effects of lipoxygenase-derived peroxides on the copper-initiated oxidation of LDL. Biochem J 1992; 282: 631-4