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 extensiv ely (about 95%) without a significant difference between healthy volun teers and cancer patients. At clinically relevant concentrations (0.1 - 6 muM) the binding was found to be concentration independent, indica ting nonspecific hydrophobic binding. Human serum albumin and alpha1-a cid glycoprotein were found to contribute about equally to the binding , with a minor contribution from lipoproteins. None of the drugs commo nly coadministered with taxol (dexamethasone, diphenhydramine, ranitid ine, doxorubicin, 5-fluorouracil and cisplatin) altered the binding of taxol significantly. The protein binding of taxol was found to dramat ically decrease the red blood cell uptake of taxol.