Cyclodextrins improve oral absorption of a novel factor Xa inhibitor by interfering with interaction between the drug and bile acids in rats.
作者： Yoshimine Fujii , Masayuki Takahashi , Takako Ishiguro , Shinji Sakuma , Kaneto Uekama
DOI: 10.1111/JPHP.12137
关键词: Bioavailability 、 Chenodeoxycholic acid 、 Absorption (skin) 、 Bile acid 、 Factor Xa Inhibitor 、 Chemistry 、 Oral administration 、 Chromatography 、 Beta-Cyclodextrins 、 Cyclodextrin
摘要: Objectives Poor oral absorption of a factor Xa inhibitor, DX-9065, is partly due to the interaction with bile acids in gastrointestinal tract. The aim this study improve bioavailability DX-9065 by cyclodextrins (CyDs) capable interfering such interaction. Methods The abilities CyDs interfere between and sodium chenodeoxycholate were evaluated using equilibrium dialysis. was studied spectroscopically. Effects on examined rats. Key findings Hydroxypropyl-β-CyD γ-CyD effective as representative acid. Spectroscopic studies revealed that included into CyD cavity form inclusion complexes an acidic medium. With dissociation carboxyl group neutral medium, stability decreased extent replaced co-existing acids. average area under plasma concentration-time curve value after administration hydroxypropyl-β-CyD 2.5 times higher than alone statistical difference rats. Conclusions We suggest are useful designing formulations improved bioavailability.
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