Abstract
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 α-, β-, and γ-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.
Footnotes
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Send reprint requests to: Robert W. Townsend, Fujisawa Healthcare, Inc., Three Parkway North, Deerfield, IL 60015. E-mail:bob_townsend{at}Fujisawa.com
- Abbreviations used are::
- AUC
- area under the concentration-time curve
- Vss
- distribution volume at steady state
- CL
- clearance
- RES
- reticuloendothelial system
- Received August 21, 2000.
- Accepted January 12, 2001.
- The American Society for Pharmacology and Experimental Therapeutics
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