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The plasma lipoprotein distribution of amphotericin b lipid complex is influenced by the coat lipid content of high density lipoproteins Kennedy, Allison Louise

Abstract

The purpose of this study was to compare the human plasma lipoprotein distribution of amphotericin B (AmpB; Fungizone®) and amphotericin B lipid complex (ABLC; Abelcef®) in different human plasma samples, and subsequently determine the relationship of the drug distribution to lipid and protein composition and concentration of these separated fractions. Independent of plasma lipoprotein lipid and protein concentration, the majority of AmpB was recovered in the lipoprotein-deficient (LPD) plasma fraction following the incubation of free AmpB, while the majority of AmpB was recovered in the high-density lipoprotein (HDL) fraction following the incubation of ABLC. It was also observed that increases in HDL coat lipid content (which contains free cholesterol and phospholipid) resulted in less AmpB recovered in this fraction following the incubation of ABLC. However, increases in the total triglyceride to total protein ratio within HDL resulted in more AmpB recovered in this fraction following the incubation of free AmpB. It was further observed that when HDL coat lipid content (fC + PL) was artificially elevated by dithionitrobenzoate (DTNB), the percentage of AmpB recovered in this fraction was significantly decreased compared to controls following the incubation of ABLC. In addition, it was further observed that the majority of the AmpB recovered in the HDL fraction following the incubation of ABLC was found in the HDL₃ fraction. Taken together, these findings suggest that the HDL coat lipid content (more specifically HDL3) may be an important factor in determining which lipoprotein amphotericin B associates with following the incubation of ABLC. These results may be an important consideration when evaluating the pharmacokinetics, toxicity and activity of these compounds following administration to patients with altered high-density lipoprotein profiles, patients such as those with cancer, liver and kidney disease, and patients with HIV/AIDS.

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