Does Adriamycin Undergo an Enterohepatic Circulation?

Abstract

Abstract

To determine whether adriamycin (ADR) and/or its metabolites undergo an enterohepatic circulation following an iv administration, anesthetized rats with biliary and urinary fistulae were intraduodenally perfused with bile flowing from bile duct-cannulated rats which had been injected iv with 20 mg/kg [¹⁴C]ADR. During a 6-hr duodenal perfusion period, 27.3% of the ADR injected to bile donor rats was recovered as total radioactivity in the intestinal perfusate of bile recipient rats and approximately 1.6 and 0.18% were excreted in their bile and urine, respectively. The intestinal tissue of bile recipient rats contained concentrations of the total drug equivalents ranging from 1.98 μg/g in the initial portions of the duodenum to 12.21 μg/g in the distal parts of the ileum. Minimal levels were observed in the heart, lung, kidney, and liver (0.25–0.86 μg/g tissue). In order to estimate the amount of the total [¹⁴C]ADR equivalents perfused into the small intestine of the bile recipient rats, [¹⁴C]ADR 20 (mg/kg) was injected iv to a separate group of anesthetized rats in which bile was continuously collected for a 6-hr period. In these experiments, total radioactivity excreted through the biliary route accounted for 30.6% of the injected dose. These combined results indicate that approximately 10% of the total [¹⁴C]ADR equivalents eliminated in bile over a 6-hr period are reabsorbed from the lumen of the small intestine of the anesthetized rat, an amount which roughly represents 3% of the injected ADR.