Binding of anthracycline derivatives to human serum lipoproteins.
The binding of eight anthracycline analogues (including mitoxantrone) to isolated serum lipoproteins (high, low and very low density lipoproteins) was studied in order to elucidate some determinants of their interaction with lipidic structures. Serum lipoproteins were isolated by ultracentrifugation. Drug binding experiments were run by ultrafiltration at 37 degrees C and pH 7.4. Anthracycline concentrations (total and free) were determined by HPLC with fluorometric detection. All the ligands were significantly bound to the three lipoprotein classes, and for each ligand the binding increased as the lipidic fraction of lipoprotein increased. From doxorubicin to iododoxorubicin, there was a tenfold increase in lipoprotein binding (doxorubicin < mitoxantrone < epirubicin < daunorubicin < pirarubicin < aclarubicin < zorubicin < iododoxorubicin). For all the ligands studied, the extent of lipoprotein binding appears to be related to chemical determinants of lipophilicity.
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 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism*; D008942:Mitoxantrone / Q000378:metabolism; D011485:Protein Binding
D000903:Antibiotics, Antineoplastic; D008074:Lipoproteins; D008942:Mitoxantrone