Interaction between bile salts and beta-adrenoceptor antagonists

• Published in: Pharmaceutical research Vol. 12; no. 5; p. 682
• Main Authors: Grosvenor, M P, Löfroth, J E
• Format: Journal Article
• Language: English
• Published: United States 01.05.1995
• Subjects: Absorption; Adrenergic beta-Antagonists - chemistry; Adrenergic beta-Antagonists - pharmacokinetics; Bile Acids and Salts - chemistry; Bile Acids and Salts - pharmacology; Calorimetry; Drug Interactions; Hydrogen-Ion Concentration; Kinetics; Surface Properties; Temperature; Thermodynamics
• ISSN: 0724-8741
• DOI: 10.1023/A:1016203424278

The interactions between beta-adrenoceptor antagonists and bile salts were investigated by microcalorimetry. Nadolol and oxprenolol interactions with dihydroxy salts could be described by a 1:1 interaction model with the thermodynamic parameters indicating that the drugs were incorporated within the bile salt aggregates. This weak interaction was primarily hydrophobic although electrostatic attraction also played a role. Atenolol and metoprolol did not interact with the dihydroxy salts. None of the compounds interacted with trihydroxy bile salts or with salts below their aggregation concentration. Phase separation resulted when propranolol and alprenolol were present in dihydroxy salt solutions above a certain concentration with the interaction being of a hydrophobic and electrostatic nature. The implications of these results on in-vivo drug absorption are discussed.