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


METHODS
6 male 1-year-old Beagles.


METHODS
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 alpha 2-agonist activity of amitraz, and were reversed by low doses of atipamezole (50 micrograms/kg, IM), a potent alpha 2-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.


CONCLUSIONS
Atipamezole can be administered i.m. to dogs with severe amitraz poisoning to reverse all the effects observed.
Centre National d'Informations Toxicologiques Veterinaires, Ecole Nationale Vétérinaire de Lyon, France.
C
C
Hugnet
F
F
Buronrosse
X
X
Pineau
J L
JL
Cadoré
G
G
Lorgue
P J
PJ
Berny
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007306:Insecticides / Q000493:pharmacokinetics* / Q000633:toxicity*; D007328:Insulin / Q000097:blood; D008297:Male; D011041:Poisoning / Q000097:blood / Q000503:physiopathology; D011187:Posture; D013997:Time Factors; D014052:Toluidines / Q000493:pharmacokinetics* / Q000633:toxicity*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000931:Antidotes; D001786:Blood Glucose; D007093:Imidazoles; D007306:Insecticides; D007328:Insulin; D014052:Toluidines; C050701:atipamezole; D015016:Yohimbine; C014983:amitraz