Treatment of experimental invasive aspergillosis with novel amphotericin b/cholesterol-sulfate complexes

Thomas F. Patterson, Peggy Miniter, Jan Dijkstra, Francis C. Szoka, John L. Ryan, Vincent T. Andriole

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

An immunosuppressed rabbit model of invasive aspergillosiswasused to evaluate a novel micellar preparation of cholesterol sulfate complexedto amphotericin B. The acute LDso of amphotericin B-deoxycholate was 5.1 mg/kg versus 20 mg/kg for the amphotericin/cholesterol-sulfate complexes. Amphotericin B-deoxycholate giveniv at a dose of 1.5 mg/kg wasmore effective in sterilizing liverand kidneythan the amphotericin/cholesterolsulfate complexes given iv at 1.5-4.5 mg/kg, but infection persisted in the lungs of all rabbits treated with those doses. Infection persisted even when the rabbits weregiven a lethal dose of amphotericin B-deoxycholate (4.5 mg/kg), but a dose of 15 mg/kg of the amphotericin/cholesterol-sulfate complexessterilized tissues and was associated with no acute lethality. Equivalent doses of the amphotericin/cholesterol-sulfate complexeswere lesseffectivethan amphotericin B-deoxycholate, but a fourfold decreasein acute lethality improvedthe therapeutic index of amphotericin B. The amphotericin/cholesterol-sulfate complexesappear to be an improvedmeans of amphotericin Bdeliveryand may improve therapy for invasive aspergillosis.

Original languageEnglish (US)
Pages (from-to)717-724
Number of pages8
JournalJournal of Infectious Diseases
Volume159
Issue number4
DOIs
StatePublished - Apr 1989
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Treatment of experimental invasive aspergillosis with novel amphotericin b/cholesterol-sulfate complexes'. Together they form a unique fingerprint.

Cite this