| Item type |
デフォルトアイテムタイプ_（フル）(1) |
| 公開日 |
2023-03-18 |
| タイトル |
|
|
タイトル |
First-pass metabolism of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl]aminoacetic acid), a novel elastase inhibitor, in rats |
|
言語 |
en |
| 作成者 |
Watanabe, Fumiko
Sato, Masahiko
Kato, Akiko
Murakami, Teruo
Higashi, Yutaka
Yata, Noboru
|
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 権利情報 |
|
|
権利情報 |
© The Pharmaceutical Society of Japan |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
ONO-5046 |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
elastase inhibitor |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
first-pass metabolism |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
intestinal first-pass metabolism |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
hepatic extraction ratio |
| 主題 |
|
|
主題Scheme |
Other |
|
主題 |
rat |
| 内容記述 |
|
|
内容記述 |
The first-pass metabolism in the intestine and liver of ONO-5046 (N-[2-[4-(2, 2-dimethylpropionyloxy)phenylsulfonylamino]benzoyl]aminoacetic acid), a newly synthesized elastate inhibitor, was separately estimated in rats. When ONO-5046 solution was administered into the whole intestine via the bile duct at a dose of 5 μmol/rat, the extent of bioavailability was only 1.5%. A small but significant increase in the bioavailability with an increase in the dose suggested marked first-pass metabolism with a saturable process. Hepatic first-pass metabolism was estimated by determining the hepatic extraction ratio of ONO-5046 after administration into the portal vein at two different infusion rates (5 μmol/kg/9 min or 5 μmol/kg/20 s). The extraction ratio was relatively small and constant (about 20%) under 2 different infusion rates of the drug. Intestinal first-pass metabolism was estimated by determining the drug recovery in the measenteric plasma after administering the drug into the intestinal loop in situ (mesenteric blood collecting method in situ). The recovery percentage of ONO-5046 in the mesenteric plasma was small (2.58±0.04% at a dose of 1 μmol/rat), and the remaining ONO-5046 recovered in the mesenteric plasma and in the intestinal loop was a metabolite of ONO-5046 (EI-601, N-[2-[(4-hydroxyphenyl)sulfonylamino]benzoyl]aminoacetic acid). Recovery percentage of ONO-5046 in the mesenteric plasma increased significantly with an increase in the dose, although the recovery percentage was still low, even at a higher dose (9.55±1.17% of dose at a dose of 5 μmol/rat). These results indicate that the low oral bioavailability of ONO-5046 in vivo is mainly due to the marked intestinal first-pass metabolism, including the metabolism in the intestinal fluid, and the dose-dependent oral bioavailability was derived from the saturable intestinal first-pass metabolism. |
|
言語 |
en |
| 出版者 |
|
|
出版者 |
The Pharmaceutical Society of Japan |
| 言語 |
|
|
言語 |
eng |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
10.1248/bpb.20.392 |
| 関連情報 |
|
|
|
識別子タイプ |
PMID |
|
|
関連識別子 |
9145216 |
| 関連情報 |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.1248/bpb.20.392 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
1347-5215 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
0918-6158 |
| 収録物識別子 |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA11696048 |
| 開始ページ |
|
|
開始ページ |
392 |
| 書誌情報 |
Biological and Pharmaceutical Bulletin
Biological and Pharmaceutical Bulletin
巻 20,
号 4,
p. 392-396,
発行日 1997-04-15
|
| 旧ID |
46831 |
20_392.pdf (846.6 KB)
