PT - JOURNAL ARTICLE AU - Ryoko Yumoto AU - Teruo Murakami AU - Yuko Nakamoto AU - Risa Hasegawa AU - Junya Nagai AU - Mikihisa Takano TI - Transport of Rhodamine 123, a P-Glycoprotein Substrate, across Rat Intestine and Caco-2 Cell Monolayers in the Presence of Cytochrome P-450 3A-Related Compounds DP - 1999 Apr 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 149--155 VI - 289 IP - 1 4099 - http://jpet.aspetjournals.org/content/289/1/149.short 4100 - http://jpet.aspetjournals.org/content/289/1/149.full SO - J Pharmacol Exp Ther1999 Apr 01; 289 AB - Effects of cytochrome P-450 3A- and P-glycoprotein (P-gp)-related compounds, erythromycin, midazolam, ketoconazole, verapamil, and quinidine, on transport of rhodamine 123 (Rho-123), a P-gp substrate, were studied in rat intestine and in Caco-2 cells. Ileum was mainly used in rat studies because this segment showed greater P-gp-mediated Rho-123 transport. In an in vitro everted rat ileum, all the compounds examined significantly inhibited the transport of Rho-123 from serosal to mucosal surfaces across the intestine, with different inhibitory potencies among these compounds. In an in vivo rat study, the exsorption of Rho-123 from blood to the intestinal lumen, which was evaluated as exsorption clearance of Rho-123 under a steady-state plasma concentration of Rho-123, was also inhibited when these compounds were added to the intestinal lumen. Similarly, transepithelial transport of Rho-123 from the basolateral to apical side across Caco-2 cell monolayers was inhibited by these compounds. A linear relationship was observed in their inhibitory potencies on Rho-123 transport between in vitro and in vivo studies using rat ileum and between studies with rat ileum and Caco-2 cells. P-gp-mediated transport across the intestine was found to be inhibited not only by P-gp-related but also by all the cytochrome P-450 3A-related compounds examined. Within experimental error, the relative inhibitory potencies were the same between the studies with rat ileum (in vivo, in vitro) and those with Caco-2 cells. Thus, it is suggested that the function of P-gp and its sensitivity to these drugs may be similar in rat intestine and Caco-2 cells. The American Society for Pharmacology and Experimental Therapeutics