Pharmacokinetics, excretion, and mass balance of 14C after administration of 14C-cholesterol labeled AmBisome to healthy volunteers

I. Bekersky, R. M. Fielding, D. E. Dressler, S. Kline, D. N. Buell, T. J. Walsh

Research output: Contribution to journalArticlepeer-review

Abstract

Amphotericin B (AmB) in small unilamellar liposomes (AmBisome) provides higher plasma concentrations and greater safety than the conventional deoxycholate formulation. The authors compared the disposition of the liposome's drug and cholesterol components by measuring AmB and radioactivity in plasma, urine, and feces for 1 week after a single 2-hour infusion of 14C-cholesterol-labeled AmBisome (2 mg/kg, 1 μCi/kg) in healthy adults (4 males, 1 female). The plasma profile of 14C-cholesterol differed from that of AmB, lacking an initial rapid disappearance phase, having a lower total clearance, and having a volume of distribution (0.13 L/kg) close to that of the plasma compartment. The biphasic disappearance and long plasma half-life (147 h) of 14C-cholesterol were similar to those of other low-clearance liposomes. This and the low clearance of 14C-cholesterol from the plasma compartment suggest that it served as a liposome marker. The plasma drug-lipid ratio fell during the study, showing that AmB was cleared from plasma more rapidly than cholesterol or liposomes and suggesting that the composition of the liposomes changed over time. 14C-radioactivity was recovered mainly in the feces (9.5% of dose), consistent with the catabolism of cholesterol to bile salts. Combined fecal and renal clearances were < 18% of total clearance, suggesting that most of the liposomal drug and lipid remained in the body 1 week after dosing. Thus, AmBisome remains in the circulation for an extended period of time while releasing AraB, resulting in its markedly altered pharmacokinetic and safety profiles.

Original languageEnglish (US)
Pages (from-to)963-971
Number of pages9
JournalJournal of clinical pharmacology
Volume41
Issue number9
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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