title: Assessment of toxicosis induced by high-dose administration of milbemycin oxime in collies.
abstract: Fifteen Collies, previously having mild reactions to ivermectin challenge (120 micrograms/kg of body weight; 20 times the recommended dosage level), were studied to evaluate the effects of milbemycin oxime administration at 5 and 10 mg/kg (10 and 20 times the manufacturer's recommended dosage). Five replicates, comprising 3 dogs each, were formed on the basis of body weight. Within replicates, each dog was randomly allocated to treatment with 5 or 10 mg of milbemycin/kg or served as a untreated control. Dogs were examined repeatedly for signs of toxicosis for 4 days after treatment and daily thereafter. Two of 5 dogs treated at 5 mg/kg (10x) developed signs of mild depression on the day of treatment, but were normal 24 hours after treatment. All 5 dogs treated at 10 mg/kg (20x) developed signs of mild depression and ataxia by 6 hours. Signs persisted for 24 hours in 3 dogs. Two of these dogs also had mydriasis, whereas 3 salivated excessively. All dogs recovered completely by day 2 after treatment. The results of this study demonstrated that Collies sensitive to the effects of 120 micrograms of ivermectin (20x)/kg show similar sensitivity to the effects of milbemycin oxine administered at 10 mg/kg (20x). We conclude that ivermectin and milbemycin commercial formulations have similar margins of safety and that milbemycin toxicosis appears to be dose-dependent in Collies with a demonstrated sensitivity to ivermectin.
authors.affiliation: Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana 61801.
authors.forename: W J
authors.initials: WJ
authors.lastname: Tranquilli
authors.forename: A J
authors.initials: AJ
authors.lastname: Paul
authors.forename: K S
authors.initials: KS
authors.lastname: Todd
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001259:Ataxia / Q000139:chemically induced / Q000662:veterinary*; D003863:Depression / Q000139:chemically induced*; D004283:Dog Diseases / Q000139:chemically induced*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D018942:Macrolides; D008297:Male; D015878:Mydriasis / Q000139:chemically induced / Q000662:veterinary; D011897:Random Allocation; D012472:Salivation / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C027837:moxidectin