Averbach A M, Stuart O A, Sugarbaker T A, Stephens A D, Fernandez-Trigo V, Shamsa F, Sugarbaker P H
Washington Cancer Institute, Washington Hospital Center, Washington D.C. 20010, USA.
J Surg Res. 1995 Sep;59(3):415-9. doi: 10.1006/jsre.1995.1184.
This pharmacokinetic study attempted to improve the exposure of gastrointestinal tract tissues to chemotherapy by increasing the transit time of a first pass of a drug through the vascular system. Bolus infusion of 9 mg mitomycin (MMC) mixed with 1 mg of MMC labeled by 50 microCi of 14C was performed in 18 mongrel dogs. Pharmacokinetics of MMC in peripheral, portal, and aortic blood were studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted a control group. In 15 dogs MMC was infused intraaortically with the catheter's tip at the level of the celiac and superior mesenteric artery. Vascular flow was controlled in four different ways for 30 min: Type I-Type IV. In Type IV the abdominal aorta and vena cava inferior were occluded after surgical exclusion of all nongastrointestinal branches of aorta. Blood samples were obtained during a 90-min period. After solubilizing the samples, 14C-labeled MMC activity was counted by a scintillation counter. For stop-flow infusion Type I, II, III, and IV, area under the curve (AUC) ratios for portal blood versus systemic circulation were 1.6:1, 2.9:1, 2.9:1, and 8.8:1, respectively (statistically significant for Types II, III, and IV). The highest value of AUC, peak MMC concentration, and lowest clearance in portal blood were achieved in SFI Type IV. Exposure to MMC was the greatest with SFI Type IV, making this type of aortic stop-flow infusion the most favorable mode of drug administration from a pharmacokinetic perspective.
这项药代动力学研究试图通过延长药物首次通过血管系统的转运时间，来提高胃肠道组织对化疗药物的暴露程度。对18只杂种犬进行了大剂量注射，将9毫克丝裂霉素（MMC）与1毫克用50微居里的14C标记的MMC混合。在不同类型的大血管闭塞情况下，研究了MMC在周围血、门静脉血和主动脉血中的药代动力学。三只接受静脉输注的犬构成对照组。在15只犬中，将MMC经主动脉内输注，导管尖端置于腹腔干和肠系膜上动脉水平。以四种不同方式控制血管血流30分钟：I型 - IV型。在IV型中，在手术排除主动脉所有非胃肠道分支后，闭塞腹主动脉和下腔静脉。在90分钟内采集血样。将样品溶解后，用闪烁计数器计数14C标记的MMC活性。对于I型、II型、III型和IV型的停流输注，门静脉血与体循环的曲线下面积（AUC）比值分别为1.6:1、2.9:1、2.9:1和8.8:1（II型、III型和IV型具有统计学意义）。IV型停流输注在门静脉血中实现了最高的AUC值、MMC峰值浓度和最低清除率。IV型停流输注时MMC的暴露量最大，从药代动力学角度来看，这种主动脉停流输注类型是最有利的给药方式。
