A differential interaction of doxorubicin and daunorubicin with human serum proteins.

The results of a comparative investigation on the interaction of doxorubicin (adriamycin) and daunorubicin with serum proteins are reported. Whereas a strong interaction occurs in vitro between doxorubicin and human serum proteins, no appreciable binding to proteins could be detected for daunorubicin under similar experimental conditions. Since the protein-bound drug is only partially dissociated by physical procedures including gel-electrophoresis, column-chromatography and solvent extraction, the formation of a covalent bond is suggested. The doxorubicin binding to serum proteins is apparently nonselective for a class of proteins; it is strongly reduced in acid conditions and slightly dependent on the ionic strength. Two tentative reaction mechanisms have been considered.