文章基本信息

标题：Disposition of DN-2327, a New Anxiolytic, in Rats, Dogs, and Monkeys
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作者：Takahiro KONDO ; Yuriko KURATA ; Kiyoshi YOSHIDA 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1995
卷号：18
期号：2
页码：330-336
DOI：10.1248/bpb.18.330
出版社：The Pharmaceutical Society of Japan
摘要：The disposition of DN-2327 after oral dosing of ¹⁴C-labeled DN-2327 ([¹⁴C]DN-2327) to rats, dogs and monkeys was studied. DN-2327 was absorbed from the small intestine after oral administration. In the plasma of these animals, a small amount of unchanged compound and M-I were detected, with M-II (a pharmacologically active metabolite) as a major component. The concentration of the unchanged compound in rat plasma attained a peak (C_max0.002μg/ml), then declined, with a half-life (t_1/2) of 3 h. T_tax, C_max and t_1/2 of DN-2327 in dogs and monkeys were 0.6 h, 0.332μg/ml and 1.5h, and 2.3h, 0.036μg/ml and 6.2h, respectively. About 60, 75 and 48% of the radioactivity dosed was absorbed in rats, dogs and monkeys, respectively, whereas the bioavailability in rats, dogs and monkeys was less than 1, 34 and 10%, respectively, indicating that DN-2327 had been subjected to the first pass effect. In rats given [¹⁴C] DN-2327 orally, the radioactivity was distributed widely in various tissues, including the brain. In the brain regions, DN-2327 and M-II were distributed and M-II was major component, indicating that the pharmacological effects of DN-2327 may depend largely on M-II. In these animals, [¹⁴C] DN-2327 was excreted in feces via bile mostly as metabolites. During repeated oral administration, DN-2327 and its metabolites did not accumulate in rat tissues, except in the kidney.
关键词：DN-2327;anxiolytic;disposition;metabolite;brain region;accumulation