A comparative pharmacology study between the intracolonic and oral routes of 5-FU administration in a colon cancer-bearing Yoshida sarcoma rat model.
We prepared a colon cancer-bearing Yoshida sarcoma rat model to examine the dose-response relationship of antitumor activity of intracolonically or orally administered 5-fluorouracil (5-FU; 45, 30, 20, 13, and 8 mg/kg). At doses of > or =20 mg/kg and > or =30 mg/kg, the 5-FU intracolonic and oral administration groups each showed a statistically significant difference in antitumor activity against the control group (P<0.05, Williams' test). A statistically significant dose-response relationship was noted in the two routes of administration, with an ED(50) value of 29 mg/kg. White blood cell count tended to decrease at high doses when 5-FU was administered intracolonically and showed a statistically significant decrease at doses of > or =30 mg/kg when 5-FU was administered orally. Regarding the time-course of body weight, even the 5-FU highest dose (45 mg/kg) intracolonic administration group showed no inhibited body weight increase compared to the control group. However, the 5-FU (> or =20 mg/kg) oral administration groups showed a statistically significant difference in body weight increase against the control group. These facts suggested that the intracolonic administration of 5-FU, while exhibiting more potent antitumor activity than that observed in oral administration, allows an extensive reduction in its toxicities compared to oral administration.
Goto
Takeshi
T
Department of Pharmacology, Jichi Medical SchoolKawachi, Tochigi, Japan.
Tomizawa
Naoko
N
Kobayashi
Eiji
E
Fujimura
Akio
A
D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use*; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D002404:Catheterization; D003106:Colon; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use*; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy* / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D006454:Hemoglobins; D005472:Fluorouracil