METABOLISM OF [C-14] AZELASTINE IN GUINEA-PIGS

A specific HPLC separation method was used to generate C-14 metabolite profiles in lung, muscle, and liver tissue and in bile, urine, and feces obtained from male guinea pigs that received a single oral dose of 1 mg/kg [C-14]azelastine. Profiles were also generated in urine and feces of animals that received a single iv dose of labeled drug. In lung and muscle tissue, azelastine (AZ) and desmethylazelastine (DAZ) were the major components of C-14 radioactivity. The amount of the amino acid metabolites (2- and 7-ACID), formed by oxidation and azepinyl ring opening, was relatively small. In the liver significant amounts of the 7-ACID were observed in addition to AZ and DAZ. The major metabolite in bile, urine, and feces was the 7-ACID, with much less AZ and DAZ present. The balance of C-14 in the form of AZ and three metabolites in excreta (percentage of dose) was: AZ, 9.7-10.5%; DAZ, 8.7-9.6%; 2-ACID, 2.9-3.0%; and 7-ACID, 43.0-54.6%. No large differences in the quantitative profile between the two dosing routes were observed.