An experimental study on the pharmacokinetics of 5-fluorouracil regional chemotherapy for pancreatic cancer.
BACKGROUND
Recently a few centers reported promising results of regional intra-arterial chemotherapy for pancreatic cancer. However, the detailed pharmacokinetics and the side effects of anticancer agents remain unclear.


METHODS
Catheters were introduced into the gastroduodenal artery and the splenic artery of dogs. In group I, arterial infusion of 5-fluorouracil (5-FU) was performed over 10 minutes. In group II, 5-FU was infused systemically. In group III, an intra-arterial infusion was repeated weekly three times. Blood samples and liver and pancreas tissue samples were obtained to determine 5-FU levels. In a subset of each group, the pancreas, duodenum, and liver were excised for histological analyses.


RESULTS
Immediately after the infusion of 5-FU, the portal level in group I was higher than that in group II. However, the mean systemic level in group I was lower than in group II. The mean tissue concentration in the pancreas in group I was significantly higher than that of group II. Histological examination revealed no microscopic alterations after treatment in all groups, including group III.


CONCLUSIONS
This fundamental study suggested that intra-arterial chemotherapy of 5-FU for pancreatic cancer allows higher regional drug delivery without adverse effects on normal regions of the pancreas, the duodenum, and the liver.
Mitsutsuji
Masaaki
M
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kobe University, Japan.
Suzuki
Yasuyuki
Y
Iwanaga
Yasuhiro
Y
Fujino
Yasuhiro
Y
Tanioka
Yasuki
Y
Kamigaki
Takashi
T
Ku
Yonson
Y
Kuroda
Yoshikazu
Y
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004285:Dogs; D004386:Duodenum / Q000187:drug effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000187:drug effects; D008297:Male; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000662:veterinary
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil