Abstract
In order to investigate the breed ideosyncracy in dogs for milbemycin D (Milbe), the drug was administered orally (1.5 or 12.5 mg/kg body weight) or intravenously (0.5 mg/kg body weight) to rough-coated collies (Collies), Shetland sheep dogs (Shelties) and Japanese mongrel dogs (mongrels), and plasma Milbe concentrations were determined. After oral administration of Milbe at a dose of 1.0 mg/kg body weight, no dogs showed any signs. Plasma levels of Milbe were higher in some Collies and Shelties than in mongrels. At a dose of 5.0 mg/kg, all 11 mongrels failed to show any sign, but all 3 Collies and 5 of 9 Shelties showed neurologic signs such as staggering, mydriasis, semicoma, lethargy and tremor. Plasma concentrations of Milbe were above 400 ng/ml in cases with the signs. Three mongrels administered 12.5 mg/kg body weight of Milbe also displayed the same neurologic signs, and had high plasma levels of Milbe. On intravenous administration at a dose of 0.5 mg/kg, there were no significant differences in pharmacokinetic parameters between the mongrel and Collie-Shelty group. The neurologic signs developed following high plasma Milbe concentrations in every dog. It was considered that the high plasma level in Collies and Shelties might be associated with the differences in the bioavailability of Milbe.
