Effect of bile acids on the binding of drugs and dyes to human albumin

• Published in: Journal of pharmacy and pharmacology Vol. 37; no. 11; p. 812
• Main Authors: Bowmer, C J, Donoghue, P G, Leong, C F, Yates, M S
• Format: Journal Article
• Language: English
• Published: England 01.11.1985
• Subjects: Bile Acids and Salts - pharmacology; Coloring Agents - metabolism; Depression, Chemical; Dialysis; Humans; In Vitro Techniques; Kinetics; Ligands; Pharmaceutical Preparations - metabolism; Phenoxybenzamine - metabolism; Protein Binding - drug effects; Serum Albumin - metabolism; Sulfadimethoxine - metabolism; Warfarin - metabolism
• ISSN: 0022-3573
• DOI: 10.1111/j.2042-7158.1985.tb04974.x

Chenodeoxycholic, cholic, deoxycholic and taurodeoxycholic acids were found to inhibit the binding of 2-(4'-hydroxybenzeneazo)benzoic acid, methyl orange, sulphadimethoxine and warfarin to human albumin. In addition, glycodeoxycholic acid inhibited the binding of sulphadimethoxine and warfarin. In contrast, these bile acids did not inhibit the binding of phenylbutazone. The extent of displacement was in the rank order of: dihydroxy acids (chenodeoxycholic and deoxycholic) greater than trihydroxy acid (cholic) greater than conjugates (glycodeoxycholic and taurodeoxycholic). Thus the introduction of polar groups into the steroid nucleus of bile acids reduces their effectiveness as binding inhibitors. Displacement was usually accompanied by a decrease in the apparent association constant which suggests that the mechanism of displacement may be competitive.