Pharmacokinetics of intravenous adriamycin for anhepatic chemotherapy during liver transplantation

Abstract

Frequent recurrence of hepatocellular carcinoma after liver transplantation indicates the necessity to eliminate patients with advanced disease and combine transplantation with some form of perioperative adjuvant chemotherapy. This study was undertaken to elucidate adriamycin pharmacokinetics for anhepatic chemotherapy during liver transplantation. Beagles of both sexes were allocated into two groups, controls (n = 4) and anhepatic animals with total hepatectomy under venovenous bypass (n = 5). In both groups, adriamycin was administered in 1 min at a dose of 1 mg/kg through the left antecubital vein and peripheral blood was obtained at intervals for up to 2 h to determine the plasma adriamycin levels. The animals were then sacrificed to determine tissue adriamycin levels in the liver, kidney, heart, lung, and skeletal muscle. Plasma adriamycin levels in anhepatic animals were significantly higher than those in controls at all measured time points after 10 min, resulting in a 50% reduction of the mean total body clearance of adriamycin compared with controls (P < 0.01). However, there was no statistically significant difference in adriamycin levels between the two groups for all measured tissues except for the liver. Despite the complete lack of hepatic function, anhepatic animals showed only a 50% reduction in total body clearance of adriamycin compared with normal controls, probably due to compensatory excretion from other organs such as the kidney. These results suggest that systemic chemotherapy with the standard dose of adriamycin may be tolerable during the anhepatic period of liver transplantation with enhanced tumoricidal effects on micrometastases.