Selective delivery of 5-fluorouracil (5-FU) to i.p. tissues using 5-FU microspheres in rats.
A new formulation has been developed for the delivery of 5-fluorouracil (5-FU) in treating peritoneal carcinomatosis. The new formulation (5-FU-MS) involves the incorporation of 5-FU into microspheres composed of a poly(glycolide-co-lactide) matrix. The incorporated 5-FU is released slowly over a 3 week period. We investigated the drug distribution and pharmacokinetics of 5-FU in rats receiving an i.p. injection of 5-FU-MS or aqueous 5-FU solution. The concentration of 5-FU was higher in the i.p. tissues (omentum and mesentery) and lower in the extraperitoneal tissues (blood plasma, lung and heart) in rats given 5-FU-MS than in rats given the aqueous 5-FU solution. Pharmacokinetic analysis showed that the area under the curve (AUC) was significantly greater in the omentum and the mesentery than in other tissues of rats given 5-FU-MS. There was no significant difference in the AUC in the tissues of rats given the aqueous 5-FU solution.
Hagiwara
A
A
First Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyo-ku, Japan.
Sakakura
C
C
Tsujimoto
H
H
Imanishi
T
T
Ohgaki
M
M
Yamasaki
J
J
Sawai
K
K
Takahashi
T
T
Fujita
T
T
Yamamoto
A
A
Muranishi
S
S
Ikada
Y
Y
D000818:Animals; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000737:chemistry / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D008863:Microspheres; D009852:Omentum; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000737:chemistry / Q000187:drug effects; D014018:Tissue Distribution
D005472:Fluorouracil