EFFECTS OF CREMOPHOR-EL ON DISTRIBUTION OF TAXOL TO SERUM-LIPOPROTEINS

The clinical formulation of the anti-tumour agent Taxol involves the u se of a mixture of ethanol and Cremophor EL. Gel electrophoresis and d ensity-gradient ultracentrifugation were used to detect effects of Tax ol infusions on serum lipoproteins. Use of the Cremophor vehicle resul ts in a decrease in the electrophoretic mobility of serum lipoproteins along with the appearance of a lipoprotein dissociation product. Thes e effects persist during a 24 h infusion and for at least 1.5 h afterw ards, and can be reproduced in vitro using purified high-density lipop rotein (HDL) or low-density lipoprotein (LDL). In control serum, Taxol binds to albumin > HDL, but after serum is exposed to Cremophor EL in vitro or in vivo substantial binding of Taxol to the lipoprotein diss ociation product(s) was observed. The latter could represent an import ant factor in taxol biodistribution.