Int J Clin Pharmacol Res 1999;19(4):117-27. Comparative study of the efficacy and tolerability of policosanol and lovastatin in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. Crespo N, Illnait J, Mas R, Fernandez L, Fernandez J, Castano G. Enrique Cabrera Hospital, Havana, Cuba.
This randomized, double-blind study was undertaken to compare the efficacy and tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6 weeks on a lipid lowering diet, 53 patients were randomized to receive either policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p < 0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did not significantly change after therapy. Policosanol, but not lovastatin, significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison between groups showed that changes in HDL-cholesterol induced by policosanol were significantly greater (p < 0.01) than those induced by lovastatin. Both treatments were safe and well tolerated. Lovastatin moderately but significantly (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin group (p < 0.01) than in the policosanol group. In conclusion, policosanol administered at 10 mg/day produces more advantageous changes in HDL-cholesterol and has a better safety and tolerability profile than lovastatin 20 mg/day.
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Int J Clin Pharmacol Res 1999;19(4):105-16. Effects of policosanol and pravastatin on lipid profile, platelet aggregation and endothelemia in older hypercholesterolemic patients. Castano G, Mas R, Arruzazabala ML, Noa M, Illnait J, Fernandez JC, Molina V, Menendez A. Medical Surgical Research Center, Havana, Cuba. dalmer@ip.etecsa.cu
This randomized, double-blind study was undertaken to compare the effects of policosanol and pravastatin administered at 10 mg/day on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk. After 6 weeks on a lipid-lowering diet, patients with low-density lipoprotein (LDL) cholesterol levels > 3.4 mmol/l were randomized to receive, under double-blind conditions, policosanol or pravastatin 10 mg tablets that were taken with the evening meal for 8 weeks. Policosanol significantly (p < 0.00001) lowered LDL-cholesterol (19.3%), total cholesterol (13.9%) and the ratios of LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol (28.3%) and total cholesterol/HDL-cholesterol (24.4%). Pravastatin significantly (p < 0.00001) lowered LDL-cholesterol (15.6%), total cholesterol (11.8%) and the ratios (p < 0.0001) of LDL-cholesterol/HDL-cholesterol (18.9%) and total cholesterol/HDL-cholesterol (15.7%). Policosanol, but not pravastatin, significantly increased (p < 0.001) levels of HDL-cholesterol (18.4%) and reduced (p < 0.01) triglycerides (14.1%). Policosanol was more effective (p < 0.05) than pravastatin in inhibiting platelet aggregation induced by all agonists and it significantly reduced (p < 0.0001) platelet aggregation induced by arachidonic acid at 1.5 and 3 mmol/l by 42.2% and 69.5%, respectively, platelet aggregation induced by collagen 0.5 microgram/ml (p < 0.05) (16.6%) and that induced by adenosine diphosphate 1 mumol/l (p < 0.01) (20.3%). Pravastatin significantly reduced (p < 0.001) (27%) only platelet aggregation induced by arachidonic acid 3 mmol/l. Both drugs significantly decreased (p < 0.00001) endothelemia levels but final values were significantly lower (p < 0.001) in the policosanol than in the pravastatin group. Both treatments were safe and well tolerated. Pravastatin significantly (p < 0.01) increased serum levels of alanine amine transferase but individual values remained within normal. Two patients on pravastatin discontinued the study because of adverse experiences (myocardial infarction and jaundice, respectively). In conclusion, the effects of policosanol (10 mg/day) on lipid profile, platelet aggregation and endothelemia in older patients with type II hypercholesterolemia and high coronary risk are more favorable than those induced by the same doses of pravastatin.
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Int J Tissue React 1999;21(3):85-92. A comparative study of policosanol Versus acipimox in patients with type II hypercholesterolemia. Alcocer L, Fernandez L, Campos E, Mas R. Department of Cardiology, Mexico General Hospital, Mexico City.
An 8-week, randomized, double-blind study comparing the efficacy and tolerability of policosanol and acipimox was conducted in patients with type II hypercholesterolemia. Prior to entry into active treatment, all patients followed a standard cholesterol-lowering diet for 12 weeks. Sixty-three patients were randomized to receive either policosanol (10 mg/day) or acipimox (750 mg/day) tablets for 8 weeks under double-blind conditions. Both groups were similar at randomization. Policosanol significantly reduced total cholesterol (p < 0.0001) (15.8%), low-density lipoprotein (LDL)-cholesterol (21%) and the ratios of LDL-cholesterol to high-density lipoprotein (HDL)-cholesterol (15.8%) and cholesterol to HDL-cholesterol (11.5%). Acipimox significantly lowered both cholesterol and LDL cholesterol by 7.5%. The percent changes of total cholesterol, LDL-cholesterol and both ratios were larger in the policosanol group than in the acipimox group. Both drugs were well tolerated. Acipimox significantly increased (p > 0.001) aspartate amino transferase levels but only four patients showed increases above the normal limit. Policosanol significantly reduced creatinine values (p > 0.05) but no patients had values out of the normal range. Four patients withdrew from the study (two from each group) but none withdrew because of adverse effects. No adverse effects were reported in the policosanol group, while five patients on acipimox reported adverse effects (hot flushes, nausea, vomiting, headache, hypochondrial pain and leg edema). These results indicate that policosanol (10 mg/day) was more effective and well tolerated than was acipimox (750 mg/day) in this study population.
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Braz J Med Biol Res 1999 Oct;32(10):1269-76. Effect of policosanol on cerebral ischemia in Mongolian gerbils. Molina V, Arruzazabala ML, Carbajal D, Valdes S, Noa M, Mas R, Fraga V, Menendez R. Department of Pharmacology, Center of Natural Products, National Center of Scientific Research, Havana, Cuba.
Policosanol is a mixture of higher aliphatic primary alcohols isolated from sugar cane wax, whose main component is octacosanol. An inhibitory effect of policosanol on platelet aggregation and cerebral ischemia in animal models has been reported. Thus, the objective of the present study was to evaluate the effect of policosanol on cerebral ischemia induced by unilateral carotid ligation and bilateral clamping and recirculation in Mongolian gerbils. Policosanol (200 mg/kg) administered immediately after unilateral carotid ligation and at 12- or 24-h intervals for 48 h significantly inhibited mortality and clinical symptoms when compared with controls, whereas lower doses (100 mg/kg) were not effective. Control animals showed swelling (tissue vacuolization) and necrosis of neurons in all areas of the brain studied (frontal cortex, hippocampus, striatum and olfactory tubercle), showing a similar injury profile. In the group treated with 200 mg/kg policosanol swelling and necrosis were significantly reduced when compared with the control group. In another experimental model, comparison between groups showed that the brain water content of control gerbils (N = 15) was significantly higher after 15 min of clamping and 4 h of recirculation than in sham-operated animals (N = 13), whereas policosanol (200 mg/kg) (N = 19) significantly reduced the edema compared with the control group, with a cerebral water content identical to that of the sham-operated animals. cAMP levels in the brain of control-ligated Mongolian gerbils (N = 8) were significantly lower than those of sham-operated animals (N = 10). The policosanol-treated group (N = 10) showed significantly higher cAMP levels (2.68 pmol/g of tissue) than the positive control (1.91 pmol/g of tissue) and similar to those of non-ligated gerbils (2.97 pmol/g of tissue). In conclusion, our results show an anti-ischemic effect of policosanol administered after induction of cerebral ischemia, in two different experimental models in Mongolian gerbils, suggesting a possible therapeutic effect in cerebral vascular disorders.
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J AOAC Int 1999 Jul-Aug;82(4):834-9. Validation of a gas chromatographic method for determining fatty alcohols that compose policosanol in five-milligram film-coated tablets. Gonzalez Canavaciolo VL, Magraner Hernandez J. National Center for Scientific Research, Center of Natural Products, Havana City, Cuba.
A gas chromatographic method using a packed column and 1-eicosanol as an internal standard was developed and validated for determination of the aliphatic fatty alcohols that compose policosanol in 5 mg film-coated tablets. The alcohols were analyzed as trimethylsilyl (TMS) derivatives, prepared with N-methyl-N-trimethylsilylfluoroacetamide. The method can detect degradation products with high retention times without interfering with the peaks of the active principle. Good linearity (correlation coefficient = 0.9996) and accuracy (recovery = 100.44%) were proven over a range of 50-150% of the nominal concentration. Within-day and between-day precisions at the nominal 100% value met the acceptance criteria (< 2%). Ruggedness was examined through an intralaboratory experimental study in which 7 operational changes were made and the observed results were quantitation, repeatability, resolution, and relative retention time. Among these results, only the relative retention time (tC28,C20) was significantly affected when the column used was 2.1 m instead of 3.1 m. Repeatability and reproducibility (r = 0.1506 and R = 0.2450, respectively) were obtained from a uniform-level interlaboratory test. The method is suitable for quality control and stability studies of these tablets.
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Physiol Behav 1999 Aug 1;67(1):1-7. Oral administration of policosanol inhibits in vitro copper ion-induced rat lipoprotein peroxidation. Menendez R, Fraga V, Amor AM, Gonzalez RM, Mas R. Pharmacology Department, Center of Natural Products, National Center for Scientific Research, Havana, Cuba.
Policosanol, a new cholesterol-lowering agent, is a mixture of higher aliphatic primary alcohols isolated from sugar cane (Saccharum officinarum L.) wax, which prevents the onset of espontaneously and experimentally induced atherosclerotic lesions in experimental models. Because the oxidation of low-density lipoprotein (LDL) may play a role in the pathogenesis of atherosclerosis, we investigate the effect of policosanol on copper oxidative susceptibility of rat lipoprotein fractions (VLDL + LDL). Rats fed normal diet were treated with policosanol (250-500 mg/kg/day) for up to 4 weeks. EDTA-free lipoprotein particles were oxidized in a cell-free system by the addition of copper ions, and conjugated dienes generation was monitored by changes of optical density at 234 nm. Thiobarbituric acid-reactive substances (TBARS) content and lysine-amino group reactivity were investigated. After administration, there was no change in cholesterol, triglycerides, and phospholipid content of lipoprotein fractions; however, policosanol significantly prolongs the lag time and reduces the propagation rate of diene generation. Also, policosanol reduces TBARS content and increases lysine reactivity in lipoprotein fractions treated with Cu2+. In conclusion, policosanol, in addition to its cholesterol-lowering effect, has other properties that enables it to reduce the potential of lipoprotein to undergo lipid peroxidation. Such effect can be considered of promissory value in the management of atherosclerosis.
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Rev Med Chil 1999 Mar;127(3):286-94. [Comparative effects of policosanol and two HMG-CoA reductase inhibitors on type II hypercholesterolemia.] [Article in Spanish.] Prat H, Roman O, Pino E. Centro Cardiovascular Hospital Clinico Universidad de Chile.
BACKGROUND: Policosanol is a new cholesterol lowering agent derived from sugar cane. AIM: To compare the cholesterol lowering efficacy of policosanol with HMG CoA inhibitors. PATIENTS AND METHODS: Patients with a LDL cholesterol over 160 mg/dl were studied. If, after 6 weeks of diet, cholesterol persisted elevated, they were doubly blind randomized to receive policosanol 10 mg/day (55 patients), lovastatin 20 mg/day (26 patients) or simvastatin 10 mg/day (25 patients). Serum cholesterol was measured again after 8 weeks of therapy. RESULTS: Initial demographic and laboratory data were similar among treatment groups. A 24% LDL cholesterol reduction was obtained with policosanol, compared with a 22% reduction with lovastatin and a 15% reduction with simvastatin. HDL cholesterol significantly increased in patients on policosanol and did not change in the other treatment groups. Adverse effects of policosanol were mild and unspecific. No changes in hepatic enzymes were observed. CONCLUSIONS: Policosanol is a safe and effective cholesterol reducing agent.
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Clin Pharmacol Ther 1999 Apr;65(4):439-47. Effects of policosanol in patients with type II hypercholesterolemia and additional coronary risk factors. Mas R, Castano G, Illnait J, Fernandez L, Fernandez J, Aleman C, Pontigas V, Lescay M. Center of Natural Products, National Center for Scientific Research, Havana City, Cuba.
INTRODUCTION: This study was undertaken to evaluate the efficacy, safety, and tolerability of policosanol, a new cholesterol-lowering drug, in patients with type II hypercholesterolemia and additional coronary risk factors. PATIENTS AND METHODS: After 5 weeks of a standard step-1 lipid-lowering diet, 437 patients were randomized to receive, under double-blind conditions, 5 mg policosanol or placebo once a day with the evening meal for 12 weeks and 10 mg policosanol or placebo for the next 12 weeks. RESULTS: Both groups were similar at randomization. Policosanol (5 and 10 mg/day) significantly reduced (P < .001) serum low-density lipoprotein cholesterol (18.2% and 25.6%, respectively) and cholesterol (13.0% and 17.4%), and it significantly raised (P < .01) high-density lipoprotein cholesterol (15.5% and 28.4%). Triglycerides remained unchanged after the first 12 weeks and lowered significantly (5.2%; P < .01) at study completion. Policosanol was safe and well tolerated, and no drug-related disturbances were observed. Two male patients who received placebo died during the study--one because of a myocardial infarction and the other because of a cardiac arrest that occurred during a surgical intervention. There were 11 serious adverse events (5.1%) in 10 patients who received placebo (4.6%), 7 of which were vascular, compared with no serious adverse events reported in patients receiving policosanol (P < .01). CONCLUSIONS: Subjects in the group treated with policosanol did not have serious adverse events during the 24-week study. This study shows that policosanol is effective, safe, and well tolerated in patients with hypercholesterolemia and concomitant coronary risk factors.
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Pharmacol Res 1999 Mar;39(3):239-45. Effects of some natural extracts on the acetylcholine release at the mouse neuromuscular junction. Re L, Barocci S, Capitani C, Vivani C, Ricci M, Rinaldi L, Paolucci G, Scarpantonio A, Leon-Fernandez OS, Morales MA. Institute of Experimental and Clinical Medicine, Laboratory of Pharmacology, University of Ancona, Ancona, 60131, Italy.
Natural extracts have been proved to be useful in different human pathological conditions. The scientific consideration of the therapeutic potential of plant extracts is still inappropriate due to the lack of both pharmacological and epidemiological basic studies. Here, we started from an electrophysiological point of view, a study on the effects of two extracts on the acetylcholine (ACh) release at the neuromuscular junction. The extracts purified from Sugar cane (policosanol) and Psidium guajava (quercetin) have been submitted to this study. The wide epidemiology of these agents suggests therapeutic potentials not yet well outlined at the basic level. Our data demonstrate some interactions in the modulation of the ACh release at the mouse neuro-muscular junction, which are well correlated with the suggested molecular mechanisms. Policosanol enhances to a small extent either the spontaneous or the evoked ACh release. Furthermore, an increase of the rate of the conformational change induced at the nicotinic receptor-channel complex by ACh is also observed. Quercetin induced a reduction of the ACh evoked release. The possibility that this effect could be ascribed to some interaction with presynaptic calcium channel is noteworthy. The results are discussed in terms of a possible interference with acetylcholinesterase by policosanol and of a presynaptic molecular action of quercetin modulating the cytosolic calcium concentration. Copyright 1999 The Italian Pharmacological Society.
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Angiology 1999 Feb;50(2):123-30. A double-blind, placebo-controlled study of the effects of policosanol in patients with intermittent claudication. Castano G, Mas R, Roca J, Fernandez L, Illnait J, Fernandez JC, Selman E. Medical Surgical Research Center, Havana City, Cuba.
This study was undertaken to evaluate the efficacy and tolerability of policosanol, a new cholesterol-lowering drug with concomitant antiplatelet effects, in patients with intermittent claudication. After a baseline period of 6 weeks, 62 patients were randomized to receive, under double-blind conditions, either placebo (31 patients) or policosanol (31), 10 mg twice daily. Walking distances in a treadmill (constant speed 3.2 km/hr, slope 10 degrees) were assessed before and after 6 months of treatment. Both groups were similar at randomization. Policosanol increased significantly (p < 0.01) the initial claudication distance from 132.5+/-13.5 m (baseline) to 205.7+/-36.3 m (after therapy) and the absolute claudication distance (p<0.0001) from 229.5+/-22.0 m to 365.4+/-46.9 m; meanwhile both variables remained unchanged in the placebo group (p<0.05). The reduction of lower limb symptoms showed a greater benefit in the policosanol group. There was no significant change in either group in the ankle/arm pressure ratio. The treatment was well tolerated. There were 10 discontinuations (seven placebo, three policosanol) from the study. Six withdrawals occurred because of adverse events (AE); all were in placebo patients. There were five serious vascular AEs in the placebo group but none in the policosanol group (p<0.05). Overall, 12/31 (38.7%) placebo patients and 3/31 (9.7%) policosanol patients experienced AEs after randomization, which showed a lesser incidence of AEs in the policosanol group (p<0.01). The present study demonstrates a beneficial effect of policosanol in patients with intermittent claudication.
