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

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12672231
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 応用薬理学・医療系薬学
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: YAMAMOTO Akira Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Professor, 薬学部, 教授 (00166779)
• Co-Investigator(Kenkyū-buntansha): FUJITA-OKA Tkuya Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University, Associate Professor, 薬学部, 助教授 (00247785)
• Project Period (FY): 2000 – 2001
• Keywords: Gastrointestinal absorption / Oral administration / Absorption enhancement / Drug efflux / Transporter / P-glycoprotein / Absorption enhancer / Pharmaceutical excipient

Research Abstract

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.