The Site-Specific Transport and Metabolism of Tacrolimus in Rat Small Intestine

The objective of this study was to evaluate the absorption of tacrolimus by means of simultaneous perfusion of intestinal lumen and blood vessels in rats. In our previous report, the permeability of tacrolimus was found to be higher in the jeju-num than in the ileum or colon, suggesting the site-dependent absorption after oral administration. However, in this article, simultaneous perfusion technique revealed that the extent of absorption into blood vessels was similar in the jejunum and the ileum regardless of the site difference in permeability as the absorption rate. In addition to the multidrug resistance-associ-ated protein-mediated efflux, cytochrome P450 (P450)-medi-ated metabolism could be a possible mechanism to explain the inconsistencies in the site dependence of tacrolimus absorp-tion. Two enzyme inhibitors, ketoconazole and midazolam