| 論文名 |
Cyclodextrins improve oral absorption of a novel factor Xa inhibitor by interfering with interaction between the drug and bile acids in rats. |
| 著者 |
Yoshimine Fujii
Masayuki Takahashi
Takako Ishiguro
Shinji Sakuma
Kaneto Uekama
Tetsumi Irie
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| キーワード |
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| 出版年月 |
1970年1月 |
| 発表先 |
J Pharm Pharmacol. 2013 Nov;65(11):1598-606. |
| WEBサイト |
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| 論文概要（和文） |
シクロデキストリンは、ラットにおける薬物と胆汁酸との相互作用を妨害することにより、新規の第Xa因子阻害剤の経口吸収を改善する。 |
| 論文概要（英文） |
Objectives: Poor oral absorption of a factor Xa inhibitor, DX-9065, is partly due to the interaction with bile acids in the gastrointestinal tract. The aim of this study is to improve the oral bioavailability of DX-9065 by cyclodextrins (CyDs) capable of interfering with such interaction. Methods: The abilities of the CyDs to interfere with the interaction between DX-9065 and sodium chenodeoxycholate were evaluated using equilibrium dialysis. The interaction between DX-9065 and the CyDs was studied spectroscopically. Effects of the CyDs on the oral absorption of DX-9065 were examined in rats. Key findings: Hydroxypropyl-β-CyD and γ-CyD were effective in interfering with the interaction between DX-9065 and sodium chenodeoxycholate as a representative bile acid. Spectroscopic studies revealed that DX-9065 was included into the CyD cavity to form inclusion complexes in an acidic medium. With dissociation of the carboxyl group of DX-9065 in a neutral medium, the stability of the complexes was decreased to such an extent that DX-9065 in the cavity is replaced with co-existing bile acids. The average area under the plasma concentration-time curve value after oral administration of DX-9065 with hydroxypropyl-β-CyD was 2.5 times higher than that of DX-9065 alone with a statistical difference in rats. Conclusions: We suggest that the CyDs are useful in designing oral formulations of DX-9065 with an improved bioavailability. |
