Vol. 29, Issue 5, 681-685, May 2001

Biodistribution of 4-[¹⁴C]Cholesterol-AmBisome following a Single Intravenous Administration to Rats

Robert W. Townsend, Anup Zutshi, and Ihor Bekersky

Fujisawa Healthcare, Inc., Deerfield, Illinois (R.W.T., I.B.); and Battelle, Columbus, Ohio (A.Z.)

A biodistribution study of 4-[¹⁴C]cholesterol-AmBisome; a unilamellar liposomal preparation of amphotericin B was conducted to support a radiolabeled human study. The radioactive plasma concentration profile (as measured in µg-Eq/ml of cholesterol) was best fit to a sum of three exponentials that yielded -, -, and -half-life estimates of 3.0 ± 0.3, 11.8 ± 3.7, and 113.4 ± 32.4 h, respectively. Clearance and the steady state volume of distribution were 4.9 ± 0.2 ml/h/kg and 341 ml/kg. Recovery data collected up through 96 h demonstrated mass balance and indicated that although the elimination profile in both urine and feces were incomplete, the dominant route of elimination (<2% in urine versus 33% in feces) was feces, presumably via biliary excretion of intact liposome and/or cholesterol. The liver, spleen, and lungs, organs of the reticuloendothelial system known 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.