Comparative evaluation of toxic effects drugs in intact animals (preclinical trials) and in modeling of disease

Abstract

In this report was carried out a comparative evaluation of lovastatin (example of miotoxic drug) under the conditions of its administration in the study of safety in intact rats and in conditions of experimental hyperlipidemia. Have been concluded 6 experimental groups of animals receiving 36 and 180 mg/kg b.w. lovastatin administration within 2 weeks. Hyperlipidemia was made by neionogenic detergent administration of triton WR-1339. It was established dose-dependent pathological changes of miotoxic markers (elevated activity of creatinekinase in 1.6-2 times, lactatdehydrogenase activity in 1.5-2 times, serum myoglobin concentration) is qualitatively worse in tests of hyperlipidemia model. Identified some changes that require a revision of the parameters of safety assessment of drugs in this group due to accumulation of biological and toxic effects.