Equilibrium binding of anthracycline cytostatics to serum albumin and small unilamellar phospholipid vesicles as measured by gel filtration.
A Sephadex G-200 gel filtration method was used to measure directly the equilibrium binding of five important anthracycline analogs to serum albumin. The order of the overall binding constant (K) in a 150 mM NaCl, 20 mM Hepes buffer (pH 7.45) was doxorubicin < daunorubicin < 4-demethoxydaunorubicin approximately 13-dihydro-4'-deoxy-4'-iododoxorubicin < 4'-deoxy-4'-iododoxorubicin for human serum albumin (K = 2.67 +/- 0.07 mM(-1) to 24.5 +/- 3.1 mM[-1]) and bovine serum albumin (K = 1.36 +/- 0.25 mM(-1) to 48.4 +/- 5.2 mM[-1]). Data were given on the pH-dependence of K. The anthracycline-albumin association reaction was compared with measurements of drug partitioning into unilamellar phospholipid membranes and octanol. The results provide important new data required for a systematic kinetic analysis of anthracycline transport in tumor cells under serum conditions in a biological system.
Demant
E J
EJ
Department of Medical Biochemistry and Genetics, Biochemistry Laboratory C, The Panum Institute, University of Copenhagen, Denmark.
Friche
E
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D000818:Animals; D018943:Anthracyclines / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism; D002417:Cattle; D002850:Chromatography, Gel; D003911:Dextrans; D006801:Humans; D007700:Kinetics; D008081:Liposomes; D051379:Mice; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism
D018943:Anthracyclines; D000970:Antineoplastic Agents; D003911:Dextrans; D008081:Liposomes; D010743:Phospholipids; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; C025614:sephadex