Pharmacokinetic evaluation of pancreatic arterial infusion chemotherapy after unification of the blood supply in an animal model.
OBJECTIVE
The purpose of this study was to investigate the potential pharmacokinetic advantage of pancreatic arterial infusion chemotherapy of 5-fluorouracil (5-FU) with temporary unification of the pancreatic blood supply for advanced pancreatic cancer in an animal model.


METHODS
Nine pigs were divided into three groups of three pigs each. 5-FU (20 mg/kg) was infused via jugular vein (group I), celiac artery (group II), and celiac artery with balloon occlusion of the superior mesenteric artery (SMA; group III). At 0, 10, 30, and 60 minutes after drug infusion, the concentrations of 5-FU were measured in plasma and tissues including the liver, pancreatic head, pancreatic uncinate process, and duodenum. Areas under the concentration-time curve (AUCs) were calculated and statistically compared.


RESULTS
The temporary unification of the pancreatic blood supply by converting from dual blood supply through the celiac artery and SMA into a single celiac arterial supply was confirmed by dye injection. Mean AUCs in the pancreas head and liver were significantly higher for groups II and III compared with group I (P < .05). In contrast, there were no significant differences in plasma 5-FU concentrations between groups. In addition, the AUC in the pancreatic uncinate process was significantly higher for group III compared with groups I and II (P < .05).


CONCLUSIONS
Pancreatic arterial infusion chemotherapy allows efficient regional drug delivery into the pancreas and liver. Importantly, the unification of the pancreatic blood supply may be required to induce maximum efficacy of arterial infusion chemotherapy for the tumor in the pancreatic uncinate process.
Tanaka
Toshihiro
T
Department of Radiology, Nara Medical University, Kashihara, Japan. toshihir@bf6.so-net.ne.jp <toshihir@bf6.so-net.ne.jp>
Yamamoto
Kiyosei
K
Sho
Masayuki
M
Nishiofuku
Hideyuki
H
Inoue
Masayoshi
M
Sueyoshi
Satoru
S
Anai
Hiroshi
H
Sakaguchi
Hiroshi
H
Nakajima
Yoshiyuki
Y
Kichikawa
Kimihiko
K
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D001158:Arteries / Q000378:metabolism* / Q000601:surgery*; D005472:Fluorouracil / Q000493:pharmacokinetics*; D006801:Humans; D007261:Infusions, Intra-Arterial; D008657:Metabolic Clearance Rate; D009928:Organ Specificity; D010179:Pancreas / Q000098:blood supply* / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil