Biodistribution of 4-[C-14]cholesterol-ambisome following a single intravenous administration to rats

A biodistribution study of 4-[C-14] cholesterol-AmBisome; a unilamellar lip osomal preparation of amphotericin B was conducted to support a radiolabele d human study. The radioactive plasma concentration profile (as measured in mug-Eq/ml of cholesterol) was best fit to a sum of three exponentials that yielded alpha-, beta-, and gamma -half-life estimates of 3.0 +/- 0.3, 11.8 +/- 3.7, and 113.4 +/- 32.4 h, respectively. Clearance and the steady stat e volume of distribution were 4.9 +/- 0.2 ml/h/kg and 341 ml/kg. Recovery d ata collected up through 96 h demonstrated mass balance and indicated that although the elimination profile in both urine and feces were incomplete, t he dominant route of elimination (< 2% in urine versus 33% in feces) was fe ces, presumably via biliary excretion of intact liposome and/or cholesterol . The liver, spleen, and lungs, organs of the reticuloendothelial system kn own for their rapid uptake of liposomes, presented with the highest levels of radioactivity. Levels in the kidney were 15% of that found in the liver and lungs.