TOXICITY OF POLICOSANOL IN BEAGLE DOGS - ONE-YEAR STUDY

Policosanol is a new chemical entity composed of 8 higher aliphatic al cohols obtained from sugar cane (Saccharum officinarum), L. wax, whose cholesterol-lowering effects have been demonstrated in experimental m odels, healthy volunteers and patients with type II hypercholesterolem ia. This study investigated the oral toxicity of policosanol administe red for 52 weeks to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in 3 experimental groups (4 ani mals/group): a control and 2 treated groups receiving policosanol at 3 0 and 180 mg/kg daily (7 days/week) by gavage. No mortality was observ ed in any group. Overall, policosanol was well tolerated throughout th e study and no toxic symptoms were observed. All groups showed similar weight gain and food consumption. Lipid profile determinations showed that policosanol decreased total cholesterol by 20% approximately fro m 8 to 52 weeks. Cholesterol-lowering effects did not wear off during the study, thus demonstrating the persistence of the effectiveness. Tr iglycerides and high density lipoprotein-cholesterol (HDL-C) were not changed significantly. No blood biochemistry or histopathological dist urbances attributable to treatment were observed. This study has shown that no drug-related toxicity was induced by policosanol administered up to 180 mg/kg/day for 52 weeks to beagle dogs. Since this dose is a pproximately 620 times higher than the maximal recommended therapeutic dose (20 mg/day) it indicates a good safety margin of this product.