Comparative serum protein binding of anthracycline derivatives.
The binding of doxorubicin, iododoxorubicin, daunorubicin, epirubicin, pirarubicin, zorubicin, aclarubicin, and mitoxantrone to 600 microM human serum albumin and 50 microM alpha 1-acid glycoprotein was studied by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by high-performance liquid chromatography (HPLC) with fluorometric detection. Binding to albumin (600 microM) varied from 61% (daunorubicin) to 94% (iododoxorubicin). The binding to alpha 1-acid glycoprotein (50 microM) was more variable, ranging from 31% (epirubicin) to 64% (zorubicin), and was essentially related to the hydrophobicity of the derivatives. Simulations showed that the total serum binding varied over a broad range from 71% (doxorubicin) to 96% (iododoxorubicin). We recently reported that the binding to lipoproteins of a series of eight anthracycline analogues could be ascribed to chemicophysical determinants of lipophilicity [2]. The present study was conducted to evaluate in vitro the contribution of albumin and alpha 1-acid glycoprotein to the total serum binding of these drugs.
Chassany
O
O
Laboratoire de Pharmacologie, Faculté de Médecine, Université Paris XII, Créteil, France.
Urien
S
S
Claudepierre
P
P
Bastian
G
G
Tillement
J P
JP
D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D009961:Orosomucoid; D012709:Serum Albumin