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Binding Study of Semotiadil and Levosemotiadil with Human Serum Albumin Using High-Performance Frontal Analysis

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Abstract

High-performance frontal analysis (HPFA) was applied to investigate the binding properties of semotiadil (R-isomer, Ca-channel blocker) and levosemotiadil (S-isomer, Ca- and Na-channel blocker), an enantiomeric pair of drugs under development, to human serum albumin (HSA). An on-line HPLC system consisting of a HPFA column, an extraction column and an analytical HPLC column was used to determine the unbound concentrations of these enantiomers. The experimental data were subjected to Scatchard analyses to estimate the binding parameters. The binding affinity of levosemo-tiadil (K=6.59×105 M-1, n=0.97) is about three-times stronger than that of semotiadil (K=2.15×105 M-1, n=0.99). These results did not change in the presence of warfarin, but were significantly decreased by the addition of diazepam, indicating that both enantiomers are bound at the diazepam site on HSA molecule.

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan

    Maria Esther Rodriguez Rosas, Akimasa Shibukawa, Yuki Yoshikawa, Yoshihiro Kuroda & Terumichi Nakagawa

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  1. Maria Esther Rodriguez Rosas
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  2. Akimasa Shibukawa
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  3. Yuki Yoshikawa
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  4. Yoshihiro Kuroda
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  5. Terumichi Nakagawa
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Rosas, M.E.R., Shibukawa, A., Yoshikawa, Y. et al. Binding Study of Semotiadil and Levosemotiadil with Human Serum Albumin Using High-Performance Frontal Analysis. ANAL. SCI. 15, 217–222 (1999). https://doi.org/10.2116/analsci.15.217

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  • DOI: https://doi.org/10.2116/analsci.15.217

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