Recovery of warfarin from an enteral nutrient formula

The in vitro recovery of warfarin from an enteral nutrient formula after filtration to remove the protein-bound fractions was determined. This study was conducted in two parts. In part 1, 0.25-, 0.50-, and 1-mL aliquots of warfarin sodium stock solution were added to 150 mL of the enteral nutrient formula Osmolite under physiologic conditions to produce warfarin concentrations of 16.7, 33.3, and 66.7 micrograms/mL. In part 2, a 0.5-mL aliquot of the warfarin sodium stock solution was added to Osmolite 100 mL-distilled water 50 mL, Osmolite 75 mL-distilled water 75 mL, and Osmolite 150 mL. The samples were filtered through a membrane that retained macromolecules while allowing warfarin to pass through, and the warfarin concentration was measured by high-performance liquid chromatography. Assays of protein-free buffered control solutions of warfarin before and after filtration indicated that no significant amount of warfarin was retained in the filtration membrane. Significantly less warfarin was recovered from full-strength Osmolite after filtering than before filtering at all warfarin concentrations tested. Significantly more warfarin was recovered from the Osmolite-distilled water solutions than from the undiluted Osmolite. These results suggest that there is some sequestering of warfarin in the macromolecular fraction of the enteral nutrient formula. The decreased recovery of warfarin from the enteral nutrient formula used in this study has potential clinical importance, but further research in humans is needed to substantiate these in vitro observations.