Acute Oral Toxicity of the Supramolecular Complex of Ivermectin

Abstract

The purpose of the research is to study the acute oral toxicity of the supramolecular complex of ivermectin. Materials and methods. The object of the study was laboratory animals kept in the vivarium of the All-Russian Scientific Research Institute of Fundamental and Applied Parasitology of Animals and Plants. The preclinical study of the ivermectin complex was carried out in accordance with “Guidelines for the Experimental (Preclinical) Study of New Pharmacological Substances”. To process the experimental data in the study of the supramolecular complex of ivermectin, the method proposed by Litchfield and Wilcoxon modified by Z. Roth was used. Acute oral toxicity was carried out with the administration of a complex of ivermectin and the substance ivermectin into the stomach for control in high doses in white mice and rats with a live weight of 18 and 160–180 g respectively. For each dose, 10 mice and 6 rats were used. The drug was administered once using a gastric tube in a doses from 40 to 350 mg/kg in terms of AS. For 14 days the general condition and behavior of animals, possible death, as well as the manifestation of symptoms of intoxication has been monitored. Results and discussion. As our studies showed, the picture of intoxication in both species (mice and rats) was comparable, and the dependence of the number of dead animals on the administered dose was also revealed. Unlike the substance ivermectin, the toxicity of the supramolecular complex is 3 times lower. The introduction of arabinogalactan into the composition of the drug helps to level the negative effect of AS (ivermectin) in the supramolecular complex preparation on the animal organism. LD50 of ivermectin substance for mice was 82.0, for rats – 165.0 mg/kg, supramolecular complex of ivermectin – 280.0 and 298.0 mg/kg respectively (according to the drug 14500 and 14598 mg/kg). According to GOST 12.1.007-76, the supramolecular complex of ivermectin belongs to hazard class 4.