[Pharmacokinetic studies on continuous intraportal 5-fluorouracil infusion].
Pharmacokinetics of 5-FU administered by continuous intraportal infusion were studied by infusing 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg of 5-FU, respectively, into the ileocecal vein for an hour. Blood samples were collected from portal vein, femoral vein and liver, and small intestine specimens were obtained at proper intervals. The rabbits were sacrificed at 120 minutes from the start of 5-FU infusion. The results were as follows: Extremely high concentrations of 5-FU in the portal vein, femoral vein and liver tissue were observed in the 5-FU group infused with 40 mg/kg. This phenomenon was suggested to rely on the effect by which the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, was saturated with a large inflow of 5-FU. FdUMP concentration of the liver was lower than that of the small intestine in all groups. These results suggest that a large dose of 5-FU infusion is effective to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion.
Matsuzaki
H
H
First Dept. of Surgery, St. Marianna University School of Medicine.
Yamamura
T
T
Hanai
A
A
Oikawa
H
H
Kikuchi
K
K
Seo
K
K
Ozasa
T
T
Akaishi
O
O
Tsukikawa
S
S
Yamaguchi
S
S
D000818:Animals; D005268:Femoral Vein / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006503:Hepatic Veins / Q000378:metabolism; D007262:Infusions, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D011169:Portal Vein / Q000378:metabolism; D011817:Rabbits
D005472:Fluorouracil