Functional modulation of drug efflux system by drug interaction and development of oral drug delivery system

药物相互作用对药物流出系统的功能调节和口服给药系统的开发

• 批准号: 12672231
• 负责人: YAMAMOTO Akira
• 金额: $ 2.5万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12672231/
• 关键词: Gastrointestinal absorption; Oral administration; Absorption enhancement; Drug efflux; Transporter; P-glycoprotein; Absorption enhancer; Pharmaceutical excipient; P糖タンパク

The effects of various surfactants and polyethylene glycol on the intestinal transport of rhodamine123, a P-gp substrate, were examined by an in vitro diffusion chamber system. The jejunal serosal-to mucosal transport (Jsm) of rhodamine123 was greater than its mucosal-to serosal transport (Jms). Nonionic surfactants (Cremophor EL, Tween80 and LM) reduced the Jsm/Jms ratio of rhodamine123, whereas its ratio was not influenced in the presence of cationic surfactant (C_<16>TAB) and anionic surfactant (SDS). Therefore, these findings suggested that charge of surfactants is possibly related to the action of these surfactants on the intestinal absorption of P-gp substrates. Polyethylene glycols with various molecular weights inhibited the Jsm flux of rhodamine123 across the rat jejunum membrane.

采用体外扩散室系统研究了不同表面活性剂和聚乙二醇对P-gp底物罗丹明123肠道转运的影响。罗丹明123空肠浆液-浆液转运（Jsm）大于其浆液-浆液转运（Jms）。非离子表面活性剂（Cremophor EL、Tween80和LM）降低了罗丹明123的Jsm/Jms比值，而阳离子表面活性剂（C_<16>TAB）和阴离子表面活性剂（SDS）的存在对其比值没有影响。因此，这些发现表明，表面活性剂的电荷可能与这些表面活性剂对P-gp底物肠道吸收的作用有关。不同分子量的聚乙二醇抑制罗丹明123在大鼠空肠膜上的Jsm通量。