Kidney- and site-selective delivery of 5-fluorouracil utilizing the absorption on the kidney surface in rats.
The present study was undertaken to elucidate the kidney- and site-selective delivery of 5-fluorouracil (5-FU) utilizing the absorption on the kidney surface in rats. An experimental system utilizing a cylindrical diffusion cell attached to the right kidney surface was established. After intravenous administration of 5-FU, the concentration of 5-FU in the right and left kidneys was almost the same and was rapidly eliminated. After right kidney surface application of 5-FU, however, the concentration of 5-FU in the right kidney was significantly higher than in the left kidney and other tissues. The 5-FU concentration in four sites of the right kidney after intravenous administration was almost the same. In contrast, 5-FU was site selectively delivered in the kidney after kidney surface application. The blood concentration of 5-FU was low (<1.7 microg/ml) until 120 min after kidney surface application. The maximum blood concentration of 5-FU after kidney surface application was much lower than after intravenous administration.
School of Pharmaceutical Sciences, Nagasaki University, Japan. kawakami@net.nagasaki-u.ac.jp
Shigeru
S
Kawakami
Tomomi
T
Horimoto
Koyo
K
Nishida
Ryu
R
Hirayama
Takahiro
T
Mukai
Mikiro
M
Nakashima
Hitoshi
H
Sasaki
Toshiyuki
T
Sakaeda
Junzo
J
Nakamura
D000042:Absorption; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil