Abstract
Milbemycin D (Milbe) concentrations in plasma and tissues of the central nervous system and some other organs were determined 3 hr after oral administration in rough-coated collies (Collies), Shetland sheep dogs (Shelties) and Japanese mongrel dogs (Mongrels), and the relationships among the plasma and tissue Milbe concentrations and neurologic signs were investigated. No mongrels administered 5.0 mg/kg body weight of Milbe showed neurologic signs, but 3 of 4 Collies and 2 of 4 Shelties thus administered and 2 of 4 mongrel dogs administered 12.5 mg/kg of Milbe developed signs such as salivation, staggering and tremor. The Milbe concentrations in dogs with neurologic signs were significantly higher than in dogs without the signs in the plasma, cerebrum, cerebellum and medulla oblongata. However, there were no significant differences in tissue/plasma ratio of Milbe concentration between the dogs with and without neurologic signs except cerebrum/plasma ratio between the mongrel 12.5 mg/kg and Collie-Shelty groups. The plasma concentrations of Milbe were significantly correlated with the concentrations in the cerebrum, cerebellum, medulla oblongata, liver and kidney. It was considered that Milbe could penetrate the brain through the blood-brain barrier depending on the plasma concentration, and might cause the neurologic signs.
