CAJ | 학술논문

目的：初步探讨新型抗肿瘤活性分子SM-1的吸收特征,为其成药性评价以及剂型设计提供研究基础。方法分别采用Caco-2细胞模型及大鼠在体肠灌流模型研究 SM-1吸收特征,并通过大鼠体内药动学研究综合评价SM-1在体内的吸收程度。结果在10~40 mg · L-1时SM-1的吸收以被动扩散为主,其双向转运过程可能与浓度无关。在25~100 mg·L-1内,SM-1的 Ka 与 Peff 差异无显著性(P >0．05),说明药物吸收无自身浓度抑制作用,SM-1的小肠吸收表现为被动扩散机制,属于高渗透性化合物。 SM-1在十二指肠吸收优于其他肠段(P<0．05),在空肠、回肠、结肠的吸收差异无显著性(P>0．05)。初步药动学研究显示,SM-1在大鼠体内绝对生物利用度为29．3%。结论 SM-1渗透性高,在肠道内吸收良好,且吸收机制主要以被动扩散为主,不受转运蛋白外排作用影响,大鼠体内绝对生物利用度较低。
목적：초보탐토신형항종류활성분자SM-1적흡수특정,위기성약성평개이급제형설계제공연구기출。방법분별채용Caco-2세포모형급대서재체장관류모형연구 SM-1흡수특정,병통과대서체내약동학연구종합평개SM-1재체내적흡수정도。결과재10~40 mg · L-1시SM-1적흡수이피동확산위주,기쌍향전운과정가능여농도무관。재25~100 mg·L-1내,SM-1적 Ka 여 Peff 차이무현저성(P >0．05),설명약물흡수무자신농도억제작용,SM-1적소장흡수표현위피동확산궤제,속우고삼투성화합물。 SM-1재십이지장흡수우우기타장단(P<0．05),재공장、회장、결장적흡수차이무현저성(P>0．05)。초보약동학연구현시,SM-1재대서체내절대생물이용도위29．3%。결론 SM-1삼투성고,재장도내흡수량호,차흡수궤제주요이피동확산위주,불수전운단백외배작용영향,대서체내절대생물이용도교저。
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.