Further studies on the kidney- and site-selective delivery of 5-fluorouracil following kidney surface application in rats.
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.
Nakamura
Junzo
J
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. junzo@net.nagasaki-u.ac.jp
Horimoto
Tomomi
T
Hirayama
Ryu
R
Mukai
Takahiro
T
Nakashima
Mikiro
M
Sasaki
Hitoshi
H
Nishida
Koyo
K
D000042:Absorption / Q000187:drug effects; D000818:Animals; D001682:Biological Availability; D004058:Diffusion / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000652:urine; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014018:Tissue Distribution / Q000502:physiology
D005472:Fluorouracil