[Pharmacokinetic studies of continuous and bolus intraportal 5-fluorouracil infusion].
We studied the pharmacokinetics of continuous and bolus intraportal 5-FU infusion. In continuous intraportal infusion group, 20 mg/kg of 5-FU was infused into ileocecal vein for an hour and the same dose was infused bolusly in bolus intraportal infusion group. Blood samples were collected from portal vein continuously and liver specimens were obtained continuously. The rabbits were sacrificed at 180 minutes from the start of infusion of 5-FU and small intestine was obtained. The results were as follows: A significantly higher concentration of 5-FU in the portal vein was observed in the continuous intraportal infusion group compared with the one-shot infusion group. But the elimination rate of 5-FU was more rapid after cessation of infusion in the continuous infusion group. The rate of FdUMP elimination in the liver tended to be lower in bolus intraportal infusion. The FdUMP concentration in the small intestine was higher in the continuous intraportal infusion group than in the bolus infusion group. In the continuous intraportal infusion group, the FdUMP concentration in the liver was lower than in the small intestine. This depended on the effect of the 5-FU catabolic enzyme, dihydrouracil dehydrogenase, which is contained in the liver in large quantities. The results suggest that in order to increase the FdUMP concentration in the liver with continuous intraportal 5-FU infusion, suppression of the effect of this enzyme is necessary.
Hanai
A
A
First Dept. of Surgery, St. Marianna University School of Medicine.
Yamamura
T
T
Matsuzaki
H
H
Oikawa
H
H
Kikuchi
K
K
Ozasa
T
T
Akaishi
O
O
Senda
T
T
Katayama
K
K
D000818:Animals; D050744:Dihydrouracil Dehydrogenase (NAD+); D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors; D011169:Portal Vein; D011817:Rabbits
D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050744:Dihydrouracil Dehydrogenase (NAD+); D005472:Fluorouracil