Further Studies on the Kidney- and Site-Selective Delivery of 5-Fluorouracil Following Kidney Surface Application in Rats

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The present study was undertaken to elucidate the kidney- and site-selective delivery of 5-fluorouracil (5-FU) following kidney surface application in rats. We selected an experimental system utilizing a cylindrical diffusion cell attached to the right kidney surface. After 5-FU was applied to this surface, approximately 60% was absorbed in 180 min. A semi-log plot of the remaining amount of 5-FU in the diffusion cell gave a straight line. The cumulative amount of urinary excretion of 5-FU for up to 180 min from the right ureter was significantly higher than that from the left ureter. On the other hand, the cumulative amount of urinary excretion of 5-FU from the right and left ureters after intravenous administration of the drug was similar. The 5-FU concentration at four sites in the right kidney after intravenous administration was also similar, while the drug was site-selectively delivered in the kidney after its surface application. 5-FU accumulated at the site under the diffusion cell was rapidly eliminated after its removal from the diffusion cell. From these results, we demonstrated that the absorption of 5-FU on the kidney surface in rats is explained mostly by passive diffusion. It was further elucidated that kidney surface application of this drug in rats results in its the kidney- and site-selective delivery.
公益社団法人日本薬学会の論文
2003-12-01