Binding of taxol to human plasma, albumin and alpha 1-acid glycoprotein.
The binding of taxol to human plasma and to individual plasma proteins was studied by equilibrium dialysis. Taxol was found to bind extensively (about 95%) without a significant difference between healthy volunteers and cancer patients. At clinically relevant concentrations (0.1-6 microM), the binding was found to be concentration independent, indicating nonspecific hydrophobic binding. Human serum albumin and alpha 1-acid glycoprotein were found to contribute about equally to the binding, with a minor contribution from lipoproteins. None of the drugs commonly coadministered with taxol (dexamethasone, diphenhydramine, ranitidine, doxorubicin, 5-fluorouracil and cisplatin) altered the binding of taxol significantly. The protein binding of taxol was found to dramatically decrease the red blood cell uptake of taxol.
Kumar
G N
GN
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston 29425.
Walle
U K
UK
Bhalla
K N
KN
Walle
T
T
D000418:Albumins / Q000378:metabolism*; D003956:Dialysis; D006801:Humans; D066298:In Vitro Techniques; D009369:Neoplasms / Q000097:blood; D009961:Orosomucoid / Q000378:metabolism*; D017239:Paclitaxel / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism*
D000418:Albumins; D009961:Orosomucoid; D017239:Paclitaxel