Metabolism of [14C]azelastine in guinea pigs

A specific HPLC separation method was used to generate 14C 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 [14C]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 14C 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 14C 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.