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14-Day Repeated Intraperitoneal Toxicity Test of Ivermectin Microemulsion Injection in Wistar Rats
Zhen Dong1,2,3, Shou-Ye Xing4, Ji-Yu Zhang1,2,3
1Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, China.
Abstract:
To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg.
Insights
Ivermectin microemulsion injection showed no deaths in rats over 14 days. The no observed adverse effect level (NOAEL) was determined to be 0.19 g/kg, indicating potential liver effects at higher doses.
Area of Science:
- Veterinary Pharmacology
- Toxicology Studies
- Drug Safety Evaluation
Background:
- Ivermectin is a widely used antiparasitic drug.
- Assessing the safety profile of new drug formulations is crucial.
- Microemulsion formulations can alter drug absorption and distribution.
Purpose of the Study:
- To evaluate the 14-day repeated dose toxicity of ivermectin microemulsion injection in Wistar rats.
- To determine the no observed adverse effect level (NOAEL) of the formulation.
- To identify potential target organs for toxicity.
Main Methods:
- 100 Wistar rats received intraperitoneal injections of ivermectin microemulsion at doses of 0.38, 0.19, and 0.1 g/kg for 14 days.
- Systematic evaluation included clinical observations, organ coefficient measurements, hematology, clinical chemistry, and histopathology.
- Liver function parameters (ALT, LDH) and liver coefficients were analyzed.
Main Results:
- No mortality was observed. Mild transient clinical signs occurred in the high-dose group.
- Significant changes in ALT and LDH were noted in male rats at the highest dose.
- Increased liver coefficients were observed in both sexes at high and medium doses.
- Histopathology suggested the liver as a potential target organ, though no significant injury was found in other major organs.
Conclusions:
- Ivermectin microemulsion injection demonstrated a favorable safety profile at lower doses.
- The no observed adverse effect level (NOAEL) was established at 0.19 g/kg.
- Potential liver effects warrant consideration at higher exposure levels.
