Absorption, distribution, metabolism, and excretion of N-octylbicycloheptene dicarboximide (MGK 264) administered dermally to rats

AbstractExperiments were conducted in four groups of rats to determine the absorption, distribution, metabolism, and excretion (ADME) patterns at different time intervals following a single or multiple dermal administration of [Hexyl-1-14C] MGK 264 (N-octylbicycloheptene dicarboximide).Two groups of fasted rats were administered [14C] MGK 264 at a single dermal dose of 10 mg/kg or at a daily dermal dosage of 10 mg/ kg of nonradiolabeled compound for 14 days followed by a single dose of 14C-labeled compound at 10 mg/kg. Each animal was administered approximately 15 μCi radioactivity.Five male rats were used in each of two groups to determine the blood kinetics of administered radioactivity following a single or multipie dermal administration at 10 mg/kg. Radioactivity peaked at approximately 6 h after both single and multiple dermal dosing, indicating slow dermal absorption. The decline of radioactivity from blood followed a monophasic elimination pattern. The half-life of blood radioactivity for both grou...