Physiological and Biochemical Responses to Repeated Administration of Ivermectin in Rabbits

Background: While ivermectin is a common antiparasitic drug used in veterinary medicine, the effects of repeated administration at therapeutic doses have not been well studied. Of particular interest is the impact of ivermectin on electrolyte balance, blood biochemistry, and oxidation-related markers in rabbits, as these animals are known to be sensitive to drug-related metabolic disturbances and side effects. Methods: A total of 10 clinically healthy adult male rabbits (1.5-2 kg) were randomly assigned to a control group with no treatment or to a treatment group receiving ivermectin subcutaneously at a dose of 0.25 mg/kg once weekly for 30 days. The animals were housed in the physiological laboratory of the University of Fallujah under controlled environmental conditions. At the end of the experiment, blood samples were collected, and serum was analyzed for electrolytes, biochemical and oxidative markers, and liver enzyme activity using established laboratory methods. Results: Repeated administration of ivermectin caused a statistically significant increase in potassium, sodium, chloride, and phosphate concentrations (P≤0.05) compared with baseline, while calcium and magnesium levels remained unchanged. Glucose, total protein, creatinine, cholesterol, and triglyceride levels increased statistically significantly (P≤0.05) compared with the control group, while albumin concentration decreased. Oxidative stress indicators showed increased levels of malondialdehyde (MDA) and decreased levels of reduced glutathione (GSH), as well as superoxide dismutase (SOD) activity. Increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity were also noted. Conclusions: Repeated administration of ivermectin at therapeutic doses at short intervals causes disturbance in blood electrolyte balance, biochemical profile, and antioxidant system in rabbits, and may also negatively impact liver and kidney functions. These results indicate the need for cautions use of the drug, preferably limited to single administration at long intervals, to minimize the risk of side effects.