FRACTIONATION OF CREMOPHOR EL DELINEATES COMPONENTS RESPONSIBLE FOR PLASMA-LIPOPROTEIN ALTERATIONS AND MULTIDRUG-RESISTANCE REVERSAL

Treatment of cancer patients with 3-h infusions of taxol formulated wi th Cremophor EL resulted in a marked decrease in the electrophoretic m obility of all plasma lipoproteins. Cremophor was fractionated by reve rse-phase chromatography to determine which components were responsibl e for this behavior. Effects of different Cremophor fractions on rever sal of multidrug resistance, amino acid transport, and cytotoxicity al so were evaluated using murine leukemia cells in culture. Lipoprotein alterations were caused by Cremophor components of intermediate hydrop hobicity, which also antagonized amino acid transport and decreased vi ability of murine leukemia cells. Cremophor components responsible for reversal of multidrug resistance were of greater hydrophobicity. The lipoprotein-altering components of Cremophor could be selectively remo ved without affecting either taxol solubilization or multidrug-resista nt reversal.