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Intravenous fat emulsion (IFE) has been used as a source of parenteral nutrition for over 40 years. More recently, IFE has also been used as a diluent for intravenous drug delivery of highly lipophilic xenobiotics such as propofol and liposomal amphotericin. The use of IFE as an antidote is most extensively studied for the treatment of local anesthetic toxicity, specifically from bupivacaine, but new applications that are being investigated and reported on include the treatment of overdose from lipophilic drugs such as calcium channel blockers, cyclic antidepressants, clomipramine, and beta adrenergic antagonists, to name a few.

Intravenous fat emulsion is composed of two types of lipids, triglycerides and phospholipids. Triglycerides are hydrophobic molecules that are formed when three fatty acids are linked to one glycerol. The fatty acid chain length varies, producing different triglycerides. The main triglycerides in IFE are linoleic, linolenic, oleic, palmitic, and stearic acids, and concentrations of these vary slightly in the different commercially available fat emulsions. These long-chain triglycerides (12 or more carbons) are extracted from safflower oil and/or soybean oil depending on the brand of the emulsion.42 Newer fat emulsions contain long-chain triglycerides in addition to medium-chain triglycerides (6–12 carbons) derived from coconut, olive, and fish oils but are currently not available in the United States.46

Phospholipids contain two fatty acids bound to glycerol along with a phosphoric acid moiety at the third hydroxyl (Fig A21–1). Phospholipids are amphipathic, that is, the nonpolar fatty acids are hydrophobic while the polar phosphate head is hydrophilic. This imparts important pharmacological properties to this carrier molecule, allowing it to solubilize nonpolar xenobiotics into the aqueous serum. The phospholipids in IFE are extracted from egg yolks.

Figure A21–1.

Biologic membranes are comprised of phospolipids that have a hyrophilic phosphoglycerol "head" and hydrophobic fatty acid "tails."

The lipids in IFE are dispersed in the serum by forming an emulsion of small lipid droplets. To create the emulsion droplets, the phospholipids form a layer around a triglyceride core. The hydrophobic fatty acid component of the phospholipid molecule is directed toward the triglycerides while the hydrophilic glycerol component is directed outward away from the triglyceride core. The presence of small amounts of glycerol, which is hydrophilic, allows the lipid droplets to be suspended as an emulsion in water and serum.

Intravenous fat emulsion is a white, milky liquid. It is sterile and nonpyrogenic with a pH of about 8 (range 6 to 9). IFEs are isotonic solutions (260–310 mOsm/L) and are available in 5%, 10%, 20%, and 30% solutions. The 30% solution should be diluted before administration. IFE can be delivered through a peripheral or central vein.42

Intravenous fat emulsions have different globule sizes depending on their uses.7 Microemulsions (mean droplet size less than 0.1 μm) are used for drug delivery. Mini-emulsions ...

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