Pharmacokinetic Evaluation of Pancreatic Arterial Infusion Chemotherapy after Unification of the Blood Supply in an Animal Model
Pharmacokinetic Evaluation of Pancreatic Arterial Infusion Chemotherapy after Unification of the Blood Supply in an Animal Model
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DOI：
10.1016/j.jvir.2009.09.027
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发表时间：
2010-01-01
影响因子：
2.9
通讯作者：
Kichikawa, Kimihiko
中科院分区：
文献类型：
--
作者：
Tanaka, Toshihiro;Yamamoto, Kiyosei;Kichikawa, Kimihiko
目的：本研究的目的是在动物模型中探讨暂时统一胰腺血供的5-氟尿嘧啶（5-FU）胰腺动脉输注化疗对晚期胰腺癌的潜在药代动力学优势。材料与方法：9头猪随机分为3组，每组3头猪。5-FU （20mg /kg）经颈静脉（I组）、腹腔动脉（II组）、腹腔动脉球囊闭塞肠系膜上动脉（SMA， III组）输注。在给药后0、10、30、60分钟，测定血浆和肝脏、胰头、胰钩突、十二指肠等组织中5-FU的浓度。计算浓度时间曲线下面积（aus）并进行统计学比较。结果：染料注射证实了胰血供由腹腔动脉和SMA双血供转变为腹腔动脉单血供的暂时性统一。II组和III组胰腺、头部和肝脏平均auc均显著高于I组（P < 0.05）。相比之下，各组间血浆5-FU浓度无显著差异。III组胰腺钩突的AUC显著高于I和II组（P < 0.05）。结论：胰腺动脉输注化疗可使药物有效地进入胰腺和肝脏。重要的是，胰腺血液供应的统一可能需要诱导动脉输注化疗对胰腺钩突肿瘤的最大疗效。
PURPOSE: 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.MATERIALS AND 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.