中国药理学通报Issue(4)：542-545,546,5.DOI:10.3969/j.issn.1001-1978.2014.04.022
基于procaspase-3激活的抗肿瘤活性分子SM-1吸收机制研究
Absorption mechanism of SM-1：a procaspase-3-activated anti-tumor agent
摘要
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.关键词
SM-1/procaspase-3/Caco-2细胞模型/在体肠灌流模型/肠吸收/绝对生物利用度Key words
SM-1/procaspase-3/Caco-2 cell model/in situ intestinal perfusion model/intestinal absorp-tion/absolute bioavailability分类
医药卫生引用本文复制引用
唐靖,罗丽娜,张海龙,郑志难,张杰,李溯,何花,丁劲松..基于procaspase-3激活的抗肿瘤活性分子SM-1吸收机制研究[J].中国药理学通报,2014,(4):542-545,546,5.基金项目
国家“十二五”重大科技专项(No 2012ZX09103101-051) （No 2012ZX09103101-051）
