Isolation-perfusion of the liver with 5-fluorouracil

Isolation-perfusion of the liver was performed in ten pigs using 5-fluorouracil administered in the perfusion circuit at doses of 100, 250, 500, and 1000 mg/kg body weight. Perfusion was performed for 60 minutes at normothermic (37 C) or hyperthermic (41 C) temperatures. One animal died shortly after perfusion. Incomplete isolation of the hepatic vasculature in two animals resulted in significant drug leakage into the systemic circulation with resulting hematologic toxicity. Perfusion with 5-fluorouracil at 1000 mg/kg produced hepatic necrosis. Perfusion with 5-fluorouracil at doses of 100, 250, or 500 mg/kg produced no hepatic toxicity except for transient elevations of hepatic enzymes and resulted in no systemic drug toxicity. Levels of 5-fluorouracil tolerated by the liver in the isolation-perfusion system were more than 1000-fold greater than the maximum drug levels achievable by routine systemic, intra-arterial, or intraperitoneal administration.