Pharmacological effects of 5-fluorouracil microspheres on peritoneal carcinomatosis in animals.
A new delivery formulation (5FU-MS) of 5-fluorouracil (5FU), 5FU incorporated in microspheres composed of poly(glycolide-co-lactide) matrix, has been developed for the treatment of peritoneal carcinomatosis, and is designed to slowly release the incorporated 5FU for 3 weeks. Intraperitoneal 5FU-MS distributed higher concentrations of 5FU to the intraperitoneal tissues, such as the omentum and the mesentery, for a longer period with lower blood plasma concentrations than did the aqueous 5FU solution in rats. In experiments using mice, the lethal toxicity, determined by the probit method, in 5FU-MS was reduced to less than half that in aqueous 5FU solution. We evaluated the therapeutic effects on peritoneal carcinomatosis induced by the intraperitoneal inoculation of B-16 PC melanoma cells. The therapeutic effects of 5FU-MS were enhanced when compared with both the equivalent doses and same toxicity doses of the aqueous 5FU solution.
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
A
A
Hagiwara
T
T
Takahashi
K
K
Sawai
C
C
Sakakura
H
H
Tsujimoto
T
T
Imanishi
M
M
Ohgaki
J
J
Yamazaki
S
S
Muranishi
A
A
Yamamoto
T
T
Fujita
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy*; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008546:Melanoma, Experimental / Q000188:drug therapy; D008643:Mesentery / Q000378:metabolism; D051379:Mice; D009852:Omentum; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D051381:Rats; D016019:Survival Analysis; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil