Pharmacological evaluation of portal venous isolation and charcoal haemoperfusion for high-dose intra-arterial chemotherapy of the pancreas

Abstract

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.