Absorption mechanism of SM-1：a procaspase-3-activated anti-tumor agent
10.3969/j.issn.1001-1978.2014.04.022
- VernacularTitle:基于procaspase-3激活的抗肿瘤活性分子SM-1吸收机制研究
- Author:
Jing TANG
;
Lina LUO
;
Hailong ZHANG
;
Zhinan ZHENG
;
Jie ZHANG
;
Su LI
;
Hua HE
;
Jinsong DING
- Publication Type:Journal Article
- Keywords:
SM-1;
procaspase-3;
Caco-2 cell model;
in situ intestinal perfusion model;
intestinal absorp-tion;
absolute bioavailability
- From:
Chinese Pharmacological Bulletin
2014;(4):542-545,546
- CountryChina
- Language:Chinese
-
Abstract:
Aim To study absorption characteristics of SM-1 , a novel anti-tumor agent , to provide a research basis for the druggability evaluation of SM-1 and formu-lation design. Methods Caco-2 cell monolayer model and in situ single-pass intestinal perfusion rat model were used to study the absorption characteristics of SM-1 , and the absorption of SM-1 in vivo was evaluated through absolute bioavailability study in rats. Results The results of cell monolayer model showed that cu-mulative absorption and efflux of SM-1 increased line-arly with concentration ( 10 ~40 mg · L-1 ) . There were no significant differences in Papp with different concentrations ( P>0. 05 ) . SM-1 was absorbed mainly through passive diffusion. The intestinal perfusion re-sults showed that Ka and Pef of SM-1 had no significant differences ( P > 0. 05 ) , when the concentrations ranged from 25 to 100 mg · L-1 . SM-1 entered the systemic circulation mainly via on passive diffusion, indicating it is a compound with high permeability. The absorption of SM-1 in duodenum was superior to other intestinal segments ( P <0. 05 ) , there were no significant differences in the jejunum, ileum and colon ( P >0. 05 ) . The absolute bioavailability of SM-1 in rats was 29. 3%. Conclusion The membrane perme-ability of SM-1 is high and it can be absorbed by intes-tine well. The absorption mechanism of SM-1 is pas-sive diffusion, and it possibly escapes from the efflux transporter protein. The absolute bioavailability of SM-1 in rats is low.
