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Pharmacokinetics and brain distribution of amitraz and its metabolites in rats.
Environmental Toxicology and Pharmacology 2018 November 24
Amitraz is an acaricide and insecticide widely used in agriculture and veterinary medicine. Although central nervous system (CNS) toxicity is one of major toxicities following oral ingestion of amitraz, the understanding of the cause of the toxicity is limited. This study evaluated the systemic and brain exposure of amitraz and its major metabolites, BTS27271, 2',4'-formoxylidide, and 2,4-dimethylaniline following administration of amitraz in male Sprague-Dawley rats. Significant metabolism of amitraz was observed following the intravenous and oral administration. Amitraz related metabolites were majority of the total exposure observed, especially following oral administration. BTS27271 had higher brain exposure than amitraz and its other metabolites, which was due to low plasma protein binding but high brain tissue binding of BTS27271. Since BTS27271 has similar or higher toxicity and α2 -adrenoreceptor agonist potency than amitraz, its exposure in brain tissues may be the major cause of CNS toxicity of amitraz in animals and humans.
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