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Effect of Glycyrrhizic Acid on Protein Binding of Diltiazem, Verapamil, and Nifedipine  

Lee, Kyoung-Jin (LOCUS Pharmaceuticals, Inc.)
Park, Hye-Jeong (College of Pharmacy, Pusan National University)
Shin, Young-Hee (College of Pharmacy, Kyungsung University)
Lee, Chi-Ho (College of Pharmacy, Pusan National University)
Publication Information
Archives of Pharmacal Research / v.27, no.9, 2004 , pp. 978-983 More about this Journal
Abstract
The effects of glycyrrhizic acid (GLZ) on protein binding of diltiazem, verapamil, and nifedipine were investigated. Protein binding studies (human serum, human serum albumin (HSA) and (X1-acid glycoprotein (AAG)) were conducted using the equilibrium dialysis method with and without addition of GLZ. The binding parameters, such as the number of moles of bound drug per mole of protein, the number of binding sites per protein molecule, and the association con-stant, were estimated using the Scatchard plot. The serum binding of nifedipine, verapamil, and diltiazem was displaced with addition of GLZ, and the decreases of Ks for serum were observed. GLZ decreased the association constants of three drugs for HSA and AAG, while the binding capacity remained similar with addition of GLZ. Although the characteristics of interaction were not clear, GLZ seemed to mainly affect HSA binding of nifedipine rather than AAG binding, while GLZ seemed to affect both AAG- and HSA-bindings of verapamil and dilt-iazem resulting in a serum binding displacement.
Keywords
Protein binding; Displacement; Glycyrrhizic acid; Diltiazem; Verapamil; Nifedipine;
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