Effects of Polyoxyethylene Alkyl Ethers on the Intestinal Transport and Absorption of Rhodamine 123: A P-glycoprotein Substrate by In Vitro and In Vivo Studies.

We examined the effects of polyoxyethylene alkyl ethers (Brijs) on the intestinal transport and absorption of rhodamine 123, a P-glycoprotein (P-gp) substrate, by in vitro and in vivo studies. Brijs increased the absorptive transport of rhodamine 123 and decreased its secretory transport in the in vitro diffusion chamber method. However, Brijs did not change the transport of 5(6)-carboxyfluorescein, a non-P-gp substrate, indicating that the effect of Brijs on the transport of drugs was P-gp substrate-specific. The effects of Brijs on rhodamine 123 transport across Caco-2 cell monolayers were also examined. Secretory transport of rhodamine 123 was enhanced and its absorptive transport was significantly reduced in the presence of Brijs. Furthermore, in the in vivo studies, Brijs also enhanced the intestinal absorption of rhodamine 123 in rats. The intestinal membrane damage produced by Brijs was also evaluated by measuring the activity of lactate dehydrogenase and the release of protein. We found almost no intestinal damage in the presence of various Brijs. These findings suggest that Brijs might inhibit the function of intestinal P-gp, thereby increasing the intestinal transport and absorption of P-gp substrates without serious intestinal membrane damage.