Sasaki Y, Kurihara M, Izumi T, Maruyama T, Shirakabe H, Kamano T, Miyasaka K, Ichiki H, Tasaka K, Orima H, Ito S, Ichinohe A
Gan To Kagaku Ryoho. 1983 Sep;10(9):2023-9.
The distribution of Adriamycin (ADM), Mitomycin C (MMC) and 7-N-(p-Hydroxyphenyl)-Mitomycin C (KW 2083) in various organs inclusiding plasma level after intraarterial or intravenous infusion was determined in mongrel dogs and experimental dogs. Similar plasma time-course of ADM was obtained with both routes, showing the maximum level at 5 minutes after infusion. The maximum level with intravenous infusion was twice as highs as that with intraarterial administration. High levels of ADM were encountered in the liver, gallbladder and kidney after proper hepatic arterial infusion, in the angular region of the stomach after left gastric arterial infusion and in the gastric antrum after right gastroepiploic arterial infusion (0.8 mg/kg). There was no significant difference in plasma levels of MMC (0.2 mg/kg) and KW 2083 (1.0 mg/kg) between intraarterial and intravenous infusion. It was of interest that MMC was hardly measurable in the liver after proper hepatic arterial infusion of 0.4 mg/kg. On the other hand, rather high level of KW 2083 was observed in the liver, gallbladder and pancreas after proper hepatic arterial infusion of 1.0 mg/kg. Hepatic necrosis around the central hepatic vein noted at the histological examination seems to be due to infusion of above-mentioned anticancer agents. It is worth mentioning that the concentration of KW 2083 in tumor tissue of the stomach of experimental dog after right gastroepiploic arterial infusion was twice as high as that in intact gastric wall. Grade IIA histological alterations of tumor cells by Oboshi and Shimosato's Classification such as vacuolation of cytoplasm and pyknosis of nuclei were noted after KW 2083 infusion.
在杂种犬和实验犬中，测定了阿霉素（ADM）、丝裂霉素C（MMC）和7-N-（对羟基苯基）-丝裂霉素C（KW 2083）在包括动脉内或静脉内输注后血浆水平在内的各种器官中的分布情况。两种给药途径的ADM血浆时程相似，输注后5分钟达到最高水平。静脉输注的最高水平是动脉内给药的两倍。在适当肝动脉输注后，肝脏、胆囊和肾脏中出现高浓度的ADM；在胃左动脉输注后，胃角区域出现高浓度的ADM；在胃网膜右动脉输注（0.8 mg/kg）后，胃窦中出现高浓度的ADM。动脉内输注和静脉内输注的MMC（0.2 mg/kg）和KW 2083（1.0 mg/kg）血浆水平无显著差异。有趣的是，在适当肝动脉输注0.4 mg/kg的MMC后，肝脏中几乎检测不到MMC。另一方面，在适当肝动脉输注1.0 mg/kg的KW 2083后，肝脏、胆囊和胰腺中观察到较高水平的KW 2083。组织学检查发现中央肝静脉周围的肝坏死似乎是由于上述抗癌药物的输注所致。值得一提的是，胃网膜右动脉输注后，实验犬胃肿瘤组织中KW 2083的浓度是完整胃壁中的两倍。KW 2083输注后，观察到肿瘤细胞出现Oboshi和Shimosato分类中的IIA级组织学改变，如细胞质空泡化和核固缩。
