Biodistribution of 4-[(14)C]cholesterol-AmBisome following a single intravenous administration to rats.
A biodistribution study of 4-[(14)C]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 microg-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 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.
Townsend
R W
RW
Fujisawa Healthcare, Inc., Three Parkway North, Deerfield, IL 60015, USA. bob.townsend@Fujisawa.com
Zutshi
A
A
Bekersky
I
I
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000008:administration & dosage*; D004337:Drug Carriers; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000935:Antifungal Agents; D002250:Carbon Radioisotopes; D004337:Drug Carriers; C068538:liposomal amphotericin B; D000666:Amphotericin B; D002784:Cholesterol