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The pharmacology of hepatic regional administration of CisplatinR (DDP) was examined in a rabbit model. Routes and modes of administration were: IV, hepatic arterial infusion (HAI), HAI with stopflow, HAI with microembolic material [collagen for embolization (CFE)], and portal vein (PV). DDP was rapidly administered, blood samples were drawn over 45 minutes, and hepatic tissue was obtained. Filterable plasma DDP levels were measured by HPLC. Hepatic DDP levels were determined by atomic absorption spectroscopy. All modes of regional administration yielded significantly higher hepatic DDP levels when compared to tissue levels following IV administration. Only the PV and HACFE routes resulted in significantly less systemic drug exposure (AUC) when compared to IV administration. These data indicate a relative pharmacologic advantage of 1.8 for HAI, 3.4 for PV, 1.8 for HAI stopflow, and 4.3 for HACFE compared to IV DDP administration. This pre-clinical study demonstrates substantial pharmacologic advantage for PV and HACFE routes of DDP administration and suggests that clinical trials based on this information be considered.
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