Stomach- and site-selective delivery of 5-fluorouracil following its application on the gastric serosal surface in rats.

The present study was undertaken to elucidate the stomach- and site-selective delivery of 5-fluorouracil (5-FU) following its application on the gastric serosal surface in rats. An experimental system utilizing a cylindrical diffusion cell attached to the gastric serosal surface was established. To evaluate the gastric distribution of 5-FU, the stomach was separated into the site under the diffusion cell (site 1) and the site not under the diffusion cell (site 2). Furthermore, the mucosal side at site 1 was separated from the serosal side. After intravenous and oral administration of 5-FU, the 5-FU concentrations at sites 1 and 2 until 240 min were similar. After gastric serosal surface application of 5-FU, however, the concentration of 5-FU at site 1 until 240 min was approximately 10-fold higher than that at site 2, and was sustained. Furthermore, the 5-FU concentration on the mucosal side at site 1 and the serosal side at site 1 were comparable after gastric serosal surface application. The blood concentration of 5-FU was low (<4.4 microg/ml) until 240 min after gastric serosal surface application. The maximum blood concentration of 5-FU after gastric serosal surface application was significantly lower than after intravenous administration. Thus, the stomach- and site-selective delivery system following application on the gastric serosal surface could be applied with anticancer drugs for the treatment of gastric cancer.