| Summary: | 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.
|
|---|
