Effects of perfluorochemical emulsion components on human albumin binding of warfarin

Warfarin binding by human albumin (HSA) is altered in the presence of a perfluorochemical (PFC) emulsion. To determine which PFC emulsion component(s) was responsible for these changes, the effects of the components on this interaction were determined. Fluorescence titrations and ultrafiltration were used to monitor the effects of the components on HSA binding of 2 and 10 micrograms/ml warfarin at room temperature. Component concentrations ranged up to that present in the emulsion except for yolk phospholipids which have limited buffer solubility. For solubility reasons, oleic acid and phospholipids were studied in the presence of pluronic F-68. At 0.5% HSA pluronic F-68 caused a significant displacement of bound warfarin, while glycerol had little effect on warfarin binding. At concentrations of 20% of that in the PFC emulsion oleic acid with pluronic F-68 caused a significant increase in warfarin binding. This was followed by a very large displacement of bound warfarin at the emulsion concentrations of oleic acid and pluronic F-68. The phospholipid component had no specific effect on warfarin binding. A combination of the 4 components had an effect very similar to that of only oleic acid with pluronic F-68. At 2% HSA the combined components caused an increase in warfarin binding while at 4% HSA the combined components had little, if any, effect on warfarin binding. Thus, changes in HSA binding of warfarin in the presence of a PFC emulsion can be attributed to the oleic acid and, to a smaller degree, pluronic F-68 components of the emulsion.