Pharmacol Res 1996 Nov-Dec;34(5-6):181-5. Effect of policosanol successive dose increases on platelet aggregation in healthy volunteers. Arruzazabala ML, Valdes S, Mas R, Fernandez L, Carbajal D. Departamento de Farmacologia, Centro Nacional de Investigaciones Cientificas, Havana, Cuba.
Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10 mg day-1) for 7 days. After this period dosage was doubled to 20 mg day-1 for the next 7 days and then again doubled to 40 mg day-1, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.
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J Pharm Pharmacol 1996 Mar;48(3):306-9. Effect of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Noa M, de la Rosa MC, Mas R. Laboratory of Histology, National Center for Scientific Research, La Habana, Cuba.
Policosanol is a new cholesterol-lowering drug isolated and purified from sugar-cane wax, which prevents the development of lipofundin-induced lesions and foam-cell formation in New Zealand rabbits and Wistar rats. This study was conducted to examine the effects of policosanol on foam-cell formation in carrageenan-induced granulomas in rats. Eighteen Wistar rats were randomly distributed in three experimental groups which received orally for 20 days Tween 20 H2O as vehicle (control group) or policosanol at 2.5 or 25 mg kg-1. At the 11th day, lipofundin was injected intraperitoneally for 8 days to induce formation of foam cells in the granuloma. At day 13, carrageenan was injected subcutaneously for granuloma induction and seven days later animals were killed. A significant reduction of the foam-cell formation in granulomas of policosanol-treated rats was observed. It is concluded that policosanol prevents the development of foam cells in carrageenan-induced granulomas (extravascular medium) in rats.
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Int J Clin Pharmacol Ther 1996 Mar;34(3):134-7. Effect of policosanol on hyperlipidemia and coronary heart disease in middle-aged patients. A 14-month pilot study. Batista J, Stusser R, Saez F, Perez B. Cardiovascular Laboratory, Havana University, Cuba.
To find out the long-term lipid-lowering efficacy of policosanol in low dose and its influence in the evolution of coronary heart disease (CHD), a pilot clinical randomized single-blind, placebo-controlled trial was conducted on 23 middle-aged outpatients, with well documented diagnosis of chronic CHD and primary or marginal hyperlipidemia. Twelve patients received policosanol tablets of 1 mg twice daily, and 11 patients placebo in the same fashion, followed with rest and stress electrocardiogram (ECG), and serum lipid blood samples by 14 months. The treated group showed significant reduction of total cholesterol in 14.8% (p < or = 0.001) and of low density lipoprotein (LDL) in 15.6% (p < or = 0.05), against non significant increase of 3% and 5.5%, respectively, in the placebo group. No patient had new coronary events in both groups, but 5 of 12 treated patients exhibited a clinical tendency to improve their CHD, in comparison with no one in the placebo group (p < or = 0.05). These findings show the effectiveness of low dose of policosanol lowering total cholesterol and LDL levels and suggest a CHD improvement in middle-aged patients with primary or marginal hyperlipidemia.
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Biol Res 1996;29(2):253-7. Effect of policosanol on the hepatic cholesterol biosynthesis of normocholesterolemic rats. Menendez R, Amor AM, Gonzalez RM, Fraga V, Mas R. Centro de Productos Naturales, Centro Nacional de Investigaciones Cientificas, La Habana, Cuba.
We have suggested previously, measuring 14C-acetate incorporation into free cholesterol, that oral administration of policosanol inhibits hepatic cholesterol biosynthesis in rats. Nevertheless, since acetate has limitations to study cholesterol synthesis in vivo, we now investigate rates of incorporation of labeled water into hepatic sterol after policosanol treatment. Absolute rates of incorporation of 3H-water in sterols were depressed by policosanol by about 20%, giving a more accurate degree of cholesterol biosynthesis inhibition in this species. Since policosanol did not inhibit labeled mevalonate incorporation into cholesterol in rat liver, we also studied the effect of policosanol on hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase. Reductase activity assayed in microsomes treated with policosanol remained unchanged, suggesting that cholesterol synthesis is not inhibited by a direct action of policosanol on this enzyme.
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Int J Clin Pharmacol Res 1996;16(2-3):67-72. Effect of policosanol on platelet aggregation in healthy volunteers. Valdes S, Arruzazabala ML, Fernandez L, Mas R, Carbajal D, Aleman C, Molina V. Center of Natural Products, National Center for Scientific Research, Cubanacan, Havana, Cuba.
Policosanol is a new drug whose cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers, and patients with type II hypercholesterolaemia. The effect of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted on healthy volunteers. This included a trial of the effects of single doses (5 to 50 mg) and a study of the effects of repeated doses administered for 7 days. In the single-dose study, the percentage of platelet aggregation in response to the threshold concentration of ADP and epinephrine measured from 8:00 to 10:00 increased significantly in the placebo group, while policosanol (5, 10, 25 and 50 mg), administered orally, inhibited the increase of platelet aggregation induced by ADP and epinephrine determined at the same time. Policosanol administered at 20 mg/day for 7 days significantly inhibited platelet aggregation induced by ADP and epinephrine, although the inhibition reached by the 10 mg/day dose tended to be less significant (p = 0.06). A modest effect (p = 0.068) on collagen-induced platelet aggregation was only observed at the highest dose (50 mg/day). The low dose (5 mg/day) was ineffective. Policosanol did not affect the coagulation time when administered at single or repeated doses. No side-effects were reported in treated or placebo groups.
