Molecular Pharmacology, Vol 16, 767-777, Copyright © 1979 by the American Society for Pharmacology and Experimental Therapeutics

Binding of Drugs to Human Serum Albumin:

XI. The Specificity of Three Binding Sites as Studied with Albumin Immobilized in Microparticles

¹ Department of Pharmaceutical Biochemistry, Biomedical Center, University of Uppsala, Box 578, S-751 23 Uppsala, Sweden

Human serum albumin can be immobilized in spherical, macroporous microparticles of polyacrylamide of about 1 µm in diameter with retention of its native properties. It has been shown that diazepam, digitoxin and warfarin independently bind to albumin and can conveniently be used as markers of three separate, discrete binding sites on albumin. A simple technique has been devised by which the capacity of about 140 drugs and other compounds to affect the binding of the radioactively labeled markers has been studied. Some drugs, e.g. antirheumatic drugs of the isopropionic acid-type, some antidiabetic agents, penicillin derivatives, benzodiazepines, tryptophan, dansylsarcosine, and suiphobromophthalein efficiently displace diazepam. Other drugs, e.g., some diuretics, sulpha drugs, phenytoin, salicylic acid and butazone derivatives, azapropazoe, bilirubin, and dansylamide displace warfarin. Displacement of digitoxin is less common. In some cases the binding of the markers is improved, e.g., tamoxifen increases the binding of warfarin. Both competitive and allosteric mechanisms are responsible for the changed binding of the markers. Some results suggest the presence of more than the three binding sites for drugs on the albumin surface studied with diazepam, digitoxin and warfarin.

Note:
ACKNOWLEDGMENTS The skillful technical assistance from Mr. Börje Berg, Miss Solveigh Höglund, Mrs. Elisabeth Tidare and Mrs. Linnéa Wallsten is gratefully acknowledged. We also thank the manufacturers and their Swedish representatives for supplying us with the drugs used.

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