Quantitative human biliary excretion of adriamycin (A)

Because of the importance of biliary excretion of Adriamycin in experimental animals and indirect evidence for its importance in man from samples of autopsy bile and abnormal plasma pharmacokinetics in patients with liver disease, this study was designed to quantify human biliary excretion of A. bile from an indwelling T tube as well as this, plasma and urine were collected over a one week period from a patient with histiocytic lymphoma receiving A therapy. His liver function and plasma pharmacokinetics were normal at the time of study. Samples were extracted with chloroform: isopropanol (1:1), separated by thinlayer chromatography, and analyzed fluorometrically for A and metabolites. Cumulative biliary excretion of A and fluorescent metabolites accounted for 40% of the administered dose compared with 13% for urinary excretion. The most prominent biliary species was A followed by adriamycinol, accounting for 17% and 9% of the administered dose respectively. Four conjugated metabolites, accounted for 7%, 4 aglycones for 5% and 2 less polar metabolites for 3%. This study substantiates our prior indirect evidence that the biliary route is the primary pathway in man for excretion of A and its fluorescent metabolites and correlates with increased toxicity in patients with liver disease. Incomplete drug recovery suggests prolonged tissue retention and/or conversion to non fluorescent metabolites.