Pharmacokinetics of the oral triazole antimycotic vibunazole in animals

Methods of assay of the oral triazole antimycotic vibunazole (BAY n 7133) in body fluids by GLC, HPTLC and by a microbiological assay are described and compared. Bioassay data of vibunazole concentrations in mice and rats are lower than those of the chemical methods, probably due to a species-dependent difference in protein binding. The pharmacokinetics of vibunazole was studied after administration to mice, rats, rabbits, beagle dogs and rhesus monkeys. Peak concentrations of 14 to 16 mg/l were found in plasma of mice after oral administration of 25 mg/kg as an aqueous suspension. After the first oral dose the mean plasma half-life was 4.8 h. After the fifth dose, plasma levels were lower and declined with a half-life of 1.2 h which may indicate enzyme induction. Signs of enzyme induction after multiple oral doses were also seen in beagle dogs but not in rhesus monkeys. After intravenous administration to one beagle dog, vibunazole plasma half-life was 1.8 h. The absolute bioavailability of oral vibunazole in the dog was estimated to be about 70%.