Some pharmacotoxic aspects of ivermectin injection formulation in donkeys (Equus asinus)

Abstract

Two studies were conducted to evaluate the toxicity of ivermectin in donkeys. In the first experiment two groups of donkeys each of six animals were subjected to fasting for 48 hours as stress and then were either treated with ivermectin injection at the recommended dose i.e. 200 g/kg (T1) or five times the recommended dose i.e. 1 mg/kg (T2) body weight for seven successive days. Animals were monitored for 15 days to evaluate any change that may occur following each treatment. Selected haematological and blood biochemical parameters were evaluated to determine any changes that may occur. In the second experiment a group of six male donkeys was subjected to a 48 hours fasting period and then animals were treated with a single subcutaneous dose of ivermectin equal to 10 times the recommended dose once and then animals were evaluated for haematological and biochemical changes, if any. In the first experiment, immediately following injection of the drug signs of intoxication appeared in animals in treatment group (T2), such as: animal fell down, roll in the ground with prominent tremors at the peripheral muscles approximately for 3 minutes, then the animal stood up and continued to feed and drink normally, before death animals refused to eat or drink for a whole day or more. Four animals out of six in T2 group died following treatment with five times the recommended dose at days 6, 8, 10 and day 11 following the first treatment. At necropsy, congestion in the main visceral organs was the prominent feature in animals. Necrosis in the liver and trabeculations in the spleen, viscous yellow fluids were also observed in kidneys and pericardium. The liver was pale yellow and the kidneys were also pale with sticky yellowish fluid inside. The pericardium contained large amount of yellowish fluid. Haematomas were observed at the injection site in all animals. Histopathological changes were observed in all select¬ed organs of ivermectin-treated animals viz: lungs, liver, kidneys, spleen and heart. Ivermectin was found to pose risks of renal and hepato-toxicity in donkeys, since the biochemical parameters of liver function (i.e. aspartate aminotransferase activity, alanine aminotransferase activity) and kidney function (urea concentration) were severely affected. Changes in biochemical parameters were more intense in donkeys from group T2 than those reported in group T1. Four animals out of six died following treatment in group T2. The level of ALT, AST, and urea were significantly elevated in donkeys from group T2 when compared to the pretreatment values. Post-mortem and Histopathological examination ensured biochemical alterations of liver and kidneys. Likewise, some haematological indices (i.e. erythrocyte count, leukocyte count and haemoglobin concentration and PCV) were also influenced. It is to be concluded that repeated administration of ivermectin injection formulation at five times the recommended dose is fatal. In the second experiment, iimmediately following treatment animals tend to be ataxic and start to circle and within 48 hours of treatment signs of intoxication started to appear viz: inability to move, salivation, and food rejection. Two animals died in the 3rd and 13th day following treatment during such period the animal tends to be ataxic, with tremors in all muscles. Non-significant increase in Hb concentration and PCV started immediately following fasting and treatment and continued up to the end of the experiment. No significant (P>0.05) change in total proteins, albumin, triglycerides and cholesterol concentration was observed following fasting and treatment. The Increase in ALT and AST concentration started following treatment to reach significance level at the 4th day of treatment, and continued to be higher up to the end of the experiment. While only significant (P<0.05) increase in urea concentration was observed during the fasting period, no significant (P>0.05) increase in urea concentration was observed in treated animals during the whole period of the experiment. No significant fluctuation in phosphorus concentration was observed during the course of the experiment. No significant change was observed in sodium and potassium concentration following treatment, while slight non-significant decrease was the only change during the course of the experiment. The results of this study demonstrate that sub-acute administration of ivermectin at five times the recommended dose for seven successive days induces toxic effects on biochemical functions which correlate well with the histopathological changes in the lung, liver, kidneys, spleen and heart of donkeys. Although the data on donkeys cannot be directly applied to horses, it may be con¬cluded that use of ivermectin may cause hazardous effects at various levels to equine species.