PHARMACOKINETICS OF ADRIAMYCIN AND CISPLATIN FOR ANHEPATIC CHEMOTHERAPY DURING LIVER-TRANSPLANTATION

We investigated the pharmacokinetics of cytotoxic anticancer agents ad ministered under anhepatic conditions. Beagle dogs underwent either a sham operation consisting of laparotomy only (control group, n = 11) o r a laparotomy and total hepatectomy under venovenous bypass (anhepati c group, n = 12). Each dog received a bolus intravenous injection of e ither Adriamycin (1 mg/kg) or cisplatin (1 mg/kg). The plasma and urin e concentrations of each drug were measured at intervals for up to 2 h after drug injection. The dogs given Adriamycin were then sacrificed to determine tissue drug concentrations in the liver (controls only), spleen, kidney, heart, lung, skeletal muscle and small intestine. The control and anhepatic groups showed similar Adriamycin profiles during the initial 5 min after drug injection. However, subsequently, the pl asma Adriamycin concentrations remained persistently higher in the anh epatic dogs than in the controls, yielding a two-fold elevation of the mean area under the concentration-time curve in the anhepatic group ( P < 0.01 vs controls). The renal clearance values did not significantl y differ between the two groups. The tissue Adriamycin concentrations in all measured organs, excluding the liver, were higher in the anhepa tic group than in the controls. In a second set of experiments with ci splatin, the plasma platinum concentrations did not significantly diff er between the two groups throughout the time course. However, the ren al clearance of platinum in the anhepatic dogs showed a fourfold incre ase compared with that in the controls (P<0.01). These pharmacokinetic data suggest that Adriamycin carries the risk of increased systemic t oxicities, while cisplatin may be associated with increased renal toxi city when administered during the anhepatic period of liver transplant ation.