Metabolism of an antiallergic agent, azelastine (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(2H)-p hthalazin one hydrochloride) in rats and guinea pigs.

The in vivo metabolism of an antiallergic agent, azelastine, (4-(p-chlorobenzyl)-2-[Nmethylperhydroazepinyl-(4)]-l-(2H)-phthalazinone hydrochloride) was examined following oral administration to rats and guinea pigs. As a result, it was found that the drug was metabolized to 4-(p-chlorobenzyl)-2-[N-methyl-7-oxo-perhydroazepinyl-(4)]l-(2H)-phthalazinone, 6-hydroxy-4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]1-(2H)-phthalazinone ( 6-hydroxyazelastine ), 7-hydroxy-4-(p-chlorobenzyl)-2-[N-methyl ~ perhydroazepinyl-(4)]-1-(2H)-phthalazinone and 4-(p-chlorobenzyl)-2-[perhydroazepinyl(4)]-1-(2H)-phthalazinone (desmethylazelastine) in these animal bodies. A part of the hydroxy derivatives of the drug was excreted into urine as their glucuronides. In addition, the incubation of azelastine with rat liver microsomes resulted in the formation of 6-hydroxyazelastine and desmethylazelastine in the presence of an NADPH-generating system. 669