Amphotericin B/emulsion admixture interactions: an approach concerning the reduction of amphotericin B toxicity.

Abstract:

:Mixing Fungizone with a fat emulsion used for nutritional purpose (Intralipid or Lipofundin ) was reported to decrease Amphotericin B (AmB) toxicity in clinical use. In an effort to understand the reason for this phenomenon, spectral and morphological analyses were done for the Fungizone and Fungizone /Lipofundin admixture (FLmix). The absorption spectra analyses showed that not only Fungizone but also FLmix presented spectra that were concentration dependent. Moreover, the spectra of FLmix remained stable until the concentration of 5 x 10(-7) M, and only at 5 x 10(-8) M did they become similar in shape to the Fungizone spectra. Morphological studies revealed that even though emulsion droplets with or without Fungizone presented the same particle size, the former was less electron dense compared with Lipofundin alone. These results suggest a kind of association between Fungizoneand Lipofundin that remains over the whole range of concentrations. This hypothesis was confirmed by in vitro studies in which FLmix presented an important selectivity against human and fungal cells compared with Fungizone. These findings suggest that parenteral emulsions should be able to reduce the AmB toxicity probably by changing the AmB self-association state by binding it with emulsion droplets.

journal_name

J Pharm Sci

authors

Egito ES,Araújo IB,Damasceno BP,Price JC

doi

10.1002/jps.10223

subject

Has Abstract

pub_date

2002-11-01 00:00:00

pages

2354-66

issue

11

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(16)31101-7

journal_volume

91

pub_type

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