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Lipophilicity of Beta‐Adrenocepter Antagonists: A New Classification Scheme for Clinical Use
Author(s) -
Northfield Susan E,
Manallack David T
Publication year - 2007
Publication title -
journal of pharmacy practice and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.222
H-Index - 22
eISSN - 2055-2335
pISSN - 1445-937X
DOI - 10.1002/j.2055-2335.2007.tb00027.x
Subject(s) - lipophilicity , pharmacodynamics , medicine , beta (programming language) , pharmacology , adverse effect , pharmacokinetics , correlation , stereochemistry , chemistry , mathematics , computer science , geometry , programming language
Background The lipophilic nature of beta‐adrenoceptor antagonists (beta‐blockers) has clinical importance as it influences pharmacokinetics, pharmacodynamics, cardioprotective actions, and adverse effects. Aim To explore the lipophilicity of a series of beta‐blockers at physiological pH (logD 7.4 ) and to compare their characteristics. Method The lipophilicity of each compound at physiological pH (logD 7.4 ) was predicted and compared to available experimental data. Results An initial comparison undertaken of logP values for 30 selected beta‐blockers against calculated logD 7.4 estimates gave a good correlation ( r 2 = 0.92; s = 0.37) indicating that the rank order of lipophilicities differs little between the neutral species and appropriate charge state at pH 7.4. Similarly, for a set of 21 beta‐blockers with measured logD 7.4 values, a good correlation was observed against calculated logD 7.4 estimates ( r 2 = 0.95; s = 0.25). Of interest was a subset of ten beta‐blockers in clinical use which have an associated lipophilicity classification listed in the Therapeutic Guidelines: Cardiovascular . Amendments may be required to this three‐class scheme in the light of the present results. Conclusion A new classification scheme is proposed comprising four lipophilic beta‐blocker classes. This new proposal could be applied clinically to make appropriate choices for patients with regard to cardioprotective effects and reducing adverse effects.