Toxicity and kinetics of amitraz in dogs

Christophe Hugnet From the Centre National d'Informations Toxicologiques Vétérinaires (Hugnet, Buronfosse, Pineau, Lorgue, Bemy) and Département de clinique des carnivores (Cadoré), Ecole Nationale Vétérinaire de Lyon, BP 83, 69280 Marcy 1'Etoile, France.

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Florence Buronfosse From the Centre National d'Informations Toxicologiques Vétérinaires (Hugnet, Buronfosse, Pineau, Lorgue, Bemy) and Département de clinique des carnivores (Cadoré), Ecole Nationale Vétérinaire de Lyon, BP 83, 69280 Marcy 1'Etoile, France.

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Xavier Pineau From the Centre National d'Informations Toxicologiques Vétérinaires (Hugnet, Buronfosse, Pineau, Lorgue, Bemy) and Département de clinique des carnivores (Cadoré), Ecole Nationale Vétérinaire de Lyon, BP 83, 69280 Marcy 1'Etoile, France.

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J. -L. Cadore From the Centre National d'Informations Toxicologiques Vétérinaires (Hugnet, Buronfosse, Pineau, Lorgue, Bemy) and Département de clinique des carnivores (Cadoré), Ecole Nationale Vétérinaire de Lyon, BP 83, 69280 Marcy 1'Etoile, France.

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Guy Lorgue From the Centre National d'Informations Toxicologiques Vétérinaires (Hugnet, Buronfosse, Pineau, Lorgue, Bemy) and Département de clinique des carnivores (Cadoré), Ecole Nationale Vétérinaire de Lyon, BP 83, 69280 Marcy 1'Etoile, France.

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Philippe J. Berny From the Centre National d'Informations Toxicologiques Vétérinaires (Hugnet, Buronfosse, Pineau, Lorgue, Bemy) and Département de clinique des carnivores (Cadoré), Ecole Nationale Vétérinaire de Lyon, BP 83, 69280 Marcy 1'Etoile, France.

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Abstract

Objective

To evaluate the toxic effects of amitraz in dogs and their reversal by various doses of atipamezole.

Animals

6 male 1-year-old Beagles.

Procedure

Dogs were given 100 mg of amitraz/kg of body weight, PO. Atipamezole was administered at 3 dose rates. Clinical examination and blood sample collection were performed regularly for 48 hours to examine biological parameters and determine the toxicokinetics of amitraz as well as the efficacy of the antidote. A specific high-performance thin layer chromatographic method was developed to determine plasma amitraz concentrations.

Results

Clinical signs of toxicosis included sedation, bradycardia, polyuria, hypothermia, and hyperglycemia, all of which could be related to the α2-agonist activity of amitraz, and were reversed by low doses of atipamezole (50 μg/kg, IM), a potent α2-antagonist, within 10 minutes after injection. Peak plasma concentrations were observed after 5 hours, and the elimination half-life was long (about 24 hours).

Conclusions

All clinical and biological effects observed during the course of amitraz poisoning could be attributed to the parent compound itself and were reversed by low doses of atipamezole. The half-life of amitraz was substantially longer than that in other studies because of the high dose administered.

Clinical Relevance

Atipamezole can be administered IM to dogs with severe amitraz poisoning to reverse all the effects observed. (Am J Vet Res 1996;57:1506-1510)

Abstract

Objective

To evaluate the toxic effects of amitraz in dogs and their reversal by various doses of atipamezole.

Animals

6 male 1-year-old Beagles.

Procedure

Dogs were given 100 mg of amitraz/kg of body weight, PO. Atipamezole was administered at 3 dose rates. Clinical examination and blood sample collection were performed regularly for 48 hours to examine biological parameters and determine the toxicokinetics of amitraz as well as the efficacy of the antidote. A specific high-performance thin layer chromatographic method was developed to determine plasma amitraz concentrations.

Results

Clinical signs of toxicosis included sedation, bradycardia, polyuria, hypothermia, and hyperglycemia, all of which could be related to the α2-agonist activity of amitraz, and were reversed by low doses of atipamezole (50 μg/kg, IM), a potent α2-antagonist, within 10 minutes after injection. Peak plasma concentrations were observed after 5 hours, and the elimination half-life was long (about 24 hours).

Conclusions

All clinical and biological effects observed during the course of amitraz poisoning could be attributed to the parent compound itself and were reversed by low doses of atipamezole. The half-life of amitraz was substantially longer than that in other studies because of the high dose administered.

Clinical Relevance

Atipamezole can be administered IM to dogs with severe amitraz poisoning to reverse all the effects observed. (Am J Vet Res 1996;57:1506-1510)

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