Metabolism of an Antiallergic Agent, Azelastine (4-(p-Chlorobenzyl)-2-[N-Methylperhydroazepinyl-(4)]- 1-(2H)-Phthalazinone Hydrochloride) in Rats and Guinea Pigs

ラットおよびモルモットにおける抗アレルギー剤 azelastine の代謝

Tatsumi Kiyoshi

Yamada Hideyuki

Yoshimura Hidetoshi

Nishizawa Yukio

Sakai Misao

Mizuo Hitoshi

Yamato Chiyuki

Hiroshima Journal of Medical Sciences

[PISSN] 0018-2052

[EISSN] 2433-7668

[NCID] AA00664312

The in vivo metabolism of an antiallergic agent, azelastine, (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(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)]-1-(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.

Metabolism

Azelastine

医学 [ 490 ]

英語

Hiroshima University School of Medicine

[ISSN] 0018-2052

[NCID] AA00664312

[PMID] 6152559