TY - JOUR
T1 - Treatment of experimental invasive aspergillosis with novel amphotericin b/cholesterol-sulfate complexes
AU - Patterson, Thomas F.
AU - Miniter, Peggy
AU - Dijkstra, Jan
AU - Szoka, Francis C.
AU - Ryan, John L.
AU - Andriole, Vincent T.
N1 - Funding Information:
Received for publication 18 July 1988 and in revised form 14 November 1988. This work was presented in part at the 88th Meeting of the American Society for Microbiology, held on 8-13 May 1988, in Miami, Florida, abstract F-86, and at the 28th Interscience Conference on Antimicrobial Agents and Chemotherapy, held on 23-26 October 1988, in Los Angeles, California, abstract 317. This work was supported in part by a Hull Cancer Research Award from the New Haven Foundation and YaleComprehensive Cancer Center to T. F. P., by grant AI-18099 from the National Institute of Allergy and Infectious Diseases to J. L. R., and by grant CA-0834l from the National Cancer Institute to V. T. A. Dr. Patterson is a Daland Fellow of the American Philosophical Society and a recipient of a National Foundation for Infectious DiseaseslJanssen Pharmaceutica Fellowship for Medical Mycology. Please address requests for reprints to Dr. Thomas F. Patterson, Department of Medicine,Section of Infectious Diseases,Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510.
PY - 1989/4
Y1 - 1989/4
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/159.4.717
DO - 10.1093/infdis/159.4.717
M3 - Article
C2 - 2926162
AN - SCOPUS:0024559833
VL - 159
SP - 717
EP - 724
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 4
ER -