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Related Experiment Video

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Lethality Bioassay Using Artemia salina L.

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Toxicity in animals: target species.

¹Technology Sciences (Europe) Limited, Concordia House, St James Business Park, Grimbald Crag Court, Knaresborough, North Yorkshire, HG5 8QB, UK. Kevin.Woodward@TSGEurope.com

Current Pharmaceutical Biotechnology

|November 2, 2011

Summary

Macrocyclic lactones like ivermectin can cause neurotoxicity in animals, especially when misused or overdosed. Certain breeds are more susceptible due to a specific gene mutation affecting drug penetration in the brain.

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Area of Science:

Veterinary Pharmacology
Toxicology
Genetics

Background:

Macrocyclic lactones, such as ivermectin, are widely used endectocides.
While safe and effective when used as directed, off-label use, misuse, or overdosing can lead to toxicity in animal patients.
Pharmacovigilance data highlights neurotoxic effects as common adverse drug reactions in overdosed animals.

Purpose of the Study:

To investigate the neurotoxic effects of macrocyclic lactones in animal patients.
To identify factors contributing to enhanced sensitivity to macrocyclic lactone toxicity.
To understand the genetic basis of P-glycoprotein deficiency and its role in adverse drug reactions.

Main Methods:

Review of pharmacovigilance data to identify clinical signs of toxicity.
Preclinical toxicity studies in animal models.
Genetic analysis to identify mutations in the MDR1 gene associated with P-glycoprotein deficiency.

Main Results:

Neurotoxic effects are the primary clinical signs observed in animals overdosed with macrocyclic lactones.
Specific subpopulations of certain species exhibit heightened sensitivity to these neurotoxic effects.
This sensitivity is linked to enhanced drug penetration into the brain due to a deficiency in P-glycoprotein, often caused by an MDR1 gene mutation.

Conclusions:

Misuse and overdosing of macrocyclic lactones can result in significant neurotoxicity in animals.
Genetic variations, specifically MDR1 gene mutations leading to P-glycoprotein deficiency, predispose certain animal populations to severe adverse drug reactions.
Understanding these genetic factors is crucial for safe and effective use of macrocyclic lactones in veterinary medicine.