Differences in human phospholipid transfer protein activity following incubation of Fungizone compared to lipid-based Amphotericin-B formulations in normolipidemic and hyperlipidemic plasma.
OBJECTIVE
To investigate how different formulations of Amphotericin-B (Amp-B) affect the activity of phospholipid transfer protein (PLTP) when incubated with hyperlipidemic and normolipidemic plasma at physiological temperature (37 degrees C).


METHODS
Six hyperlipidemic and six normolipidemic plasma samples were collected and tested for protein concentration. Equivalent protein levels (25 microg) were then tested for PLTP activity using an in vitro established kit at physiological temperature (37 degrees C). Increasing concentrations of different Amp-B formulations (1, 2, and 5 microg/mL) in the pharmacological range were then added to the plasma and tested for activity from 5 to 90 minutes. The Amp-B formulations used in the study were Fungizone, Abelcet, and AmBisome.


RESULTS
In normolipidemic plasma, PLTP activity was found to be increased by Abelcet and AmBisome but inhibited by Fungizone. In hyperlipidemic plasma, PLTP activity was found to be increased by Abelcet and AmBisome but not changed by Fungizone. The Vm value for Abelcet and AmBisome was higher than Fungizone(; although, no difference was observed in the Km values between formulations.


CONCLUSIONS
Findings suggest that lipid-based formulations of Amp-B promote the transfer of Amp-B into high-density lipoprotein fractions at a degree of increase inversely proportional to the lipid levels in the plasma.
Henderson
Ryan J
RJ
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Leon
Carlos G
CG
Wasan
Kishor M
KM
D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015153:Blotting, Western; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D006031:Glycosylation; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008081:Liposomes; D008958:Models, Molecular; D049294:Phospholipid Transfer Proteins / Q000378:metabolism*
D000935:Antifungal Agents; D004337:Drug Carriers; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008081:Liposomes; D049294:Phospholipid Transfer Proteins; D000666:Amphotericin B