Tominaga M, Ku Y, Iwasaki T, Suzuki Y, Kuroda Y, Saitoh Y
First Department of Surgery, Kobe University School of Medicine, Japan.
Br J Surg. 1997 Aug;84(8):1072-6.
A novel system of complete portal venous isolation and charcoal haemoperfusion (PVI-CHP) has been developed in an attempt to increase dose intensity while minimizing the systemic toxicity of the cytotoxic agent during intra-arterial chemotherapy of the pancreas.
Mongrel dogs were given doxorubicin (3 mg kg-1), infused over a 5-min period via the splenic artery, together with PVI-CHP (group 1; n = 5) or without PVI-CHP (group 2; n = 5). Plasma doxorubicin concentrations were determined in serial samples obtained from the inlet and outlet of the CHP filter and in samples obtained from the left jugular vein (systemic levels) for up to 30 min after initiation of drug infusion. Subsequently, specimens were obtained from the pancreas, liver and heart to determine tissue doxorubicin levels.
The mean(s.d.) peak systemic concentration of doxorubicin in group 1 was 0.78(0.03) microgram ml-1, significantly lower than that in group 2 of 3.49(1.15) micrograms ml-1 (P < 0.01). The peak concentration of doxorubicin in group 1 was significantly lower (more than 90 per cent) than that before filtration (P < 0.01). Tissue doxorubicin concentration in the pancreas was similar in both groups. However, concentrations in the liver and heart were significantly lower in group 1 than in group 2 (P < 0.05).
These results indicate that PVI-CHP can produce a significant reduction in systemic drug exposure and may allow dose intensification during intra-arterial chemotherapy for the pancreas.
已开发出一种全新的完全门静脉隔离和炭血液灌注（PVI-CHP）系统，旨在在胰腺动脉内化疗期间提高剂量强度，同时将细胞毒性药物的全身毒性降至最低。
杂种犬接受阿霉素（3毫克/千克），通过脾动脉在5分钟内输注，同时接受PVI-CHP（第1组；n = 5）或不接受PVI-CHP（第2组；n = 5）。在药物输注开始后长达30分钟的时间里，从CHP过滤器的入口和出口获取的系列样本以及从左颈静脉获取的样本（全身水平）中测定血浆阿霉素浓度。随后，从胰腺、肝脏和心脏获取标本以测定组织阿霉素水平。
第1组阿霉素的平均（标准差）全身峰值浓度为0.78（0.03）微克/毫升，显著低于第2组的3.49（1.15）微克/毫升（P < 0.01）。第1组阿霉素的峰值浓度显著低于过滤前（超过90%）（P < 0.01）。两组胰腺中的组织阿霉素浓度相似。然而，第1组肝脏和心脏中的浓度显著低于第2组（P < 0.05）。
这些结果表明，PVI-CHP可显著降低全身药物暴露，并且可能允许在胰腺动脉内化疗期间增加剂量强度。
