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Focussing Review
Application of High-Performance Frontal Analysis to Enantioselective Studies on Drug - Plasma Protein Binding |
| Akimasa Shibukawa*, Maria Esther Rodriguez Rosas and Terumichi Nakagawa |
| Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan |
Abstract:
This review article demonstrates the applicability of high-performance frontal analysis (HPFA) to the enantioselective drug - plasma protein binding study. Semotiadil (R-isomer, Ca-channel blocker) and levosemotiadil (S-isomer, Ca- and Na-channel blocker), an enantiomeric pair of drugs under development, were used as model drugs, and their binding properties to human serum albumin (HSA) and a1-acid glycoprotein (AGP) were investigated. An on-line HPLC system consisting of HPFA column, extraction column and analytical HPLC column was used to determine the unbound concentrations of these enantiomers in the binding equilibrium. The experimental data were subjected to the Scatchard analyses to estimate binding parameters. Semotiadil and levosemotiadil are bound to AGP more strongly than to HSA by 110 times and by 30 times, respectively. Semotiadil is bound to AGP 1.2 times more strongly than levosemotiadil, while levosemotiadil is bound to HSA 3 times more strongly than semotiadil. The enantioselectivity of AGP is reflected in the enantioselective protein binding of these drugs in human plasma. The enantiomer-enantiomer competitive binding study found that both enantiomers are bound at the same site on AGP molecule.
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| Keywords: | semotiadil, levosemotiadil, protein binding, albumin, AGP, high-performance frontal analysis, HPLC |
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