Excretion Pathways of Amphotericin B

Abstract

The role of the biliary system in excretion of amphotericin B was explored in a dog model that allowed either external diversion of all bile or complete biliary obstruction. In dogs with biliary diversion, which were given a single dose of amphotericin B intravenously, excretion of amphotericin B in the bile lasted for seven to 10 days and accounted for only 3% ± 2% (mean ± SD) of the dose, whereas excretion in the urine was prolonged (23–35 days) and greater (21% ± 5% of the dose); the stool contained no amphotericin B. However, bile salt depletion may have depressed bilary excretion of amphotericin B: in a dog with an intact biliary system, 19% of the dose was excreted in the stool over 11 days. In dogs given amphotericin B daily, serum levels were 19% ± 3% higher during periods of biliary obstruction than during periods of free bile flow (P < 0.05). Thus, excretion of amphotericin B in the bile (⩽ 19% of the dose) and in the urine (21% of the dose) accounted for a minority of total drug clearance. Nevertheless, prolonged excretion of amphotericin B by these routes after a single dose suggests that infrequent doses of amphotericin B may provide effective treatment for certain forms of fungal infection.