Effects of Cremophor EL on distribution of Taxol to serum lipoproteins.
The clinical formulation of the anti-tumour agent Taxol involves the use of a mixture of ethanol and Cremophor EL. Gel electrophoresis and density-gradient ultracentrifugation were used to detect effects of Taxol infusions on serum lipoproteins. Use of the Cremophor vehicle results in a decrease in the electrophoretic mobility of serum lipoproteins along with the appearance of a lipoprotein dissociation product. These effects persist during a 24 h infusion and for at least 1.5 h afterwards, and can be reproduced in vitro using purified high-density lipoprotein (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 dissociation product(s) was observed. The latter could represent an important factor in taxol biodistribution.
Sykes
E
E
Department of Clinical Pathology, William Beaumont Hospital, Royal Oak, Michigan 48073.
Woodburn
K
K
Decker
D
D
Kessel
D
D
D002499:Centrifugation, Density Gradient / Q000379:methods; D004347:Drug Interactions; D004586:Electrophoresis; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007262:Infusions, Intravenous; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D017239:Paclitaxel / Q000097:blood*; D014677:Pharmaceutical Vehicles; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D012997:Solvents; D014018:Tissue Distribution; D014461:Ultracentrifugation / Q000379:methods
D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D014677:Pharmaceutical Vehicles; D012709:Serum Albumin; D012997:Solvents; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol