Mizuma T, Masubuchi S, Awazu S
Department of Biopharmaceutics and Drug Rational Research Center, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Japan.
Pharm Res. 1999 Jan;16(1):69-73. doi: 10.1023/a:1018818728393.
To characterize the intestinal absorption of a beta-glucose conjugate of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV) and compare it to ACV and its analogues in terms of stability and transport by Na+/glucose cotransporter (SGLTI).
ACVbeta(glc) was enzymatically synthesized using cellulase. Intestinal absorption experiments were performed with rat everted small intestine. Conformation of the glucose moiety was analyzed by NMR spectroscopy.
The ACVbeta(glc) was stable on the mucosal side, and was transported to the serosal side in all regions of the small intestine. However, significant contribution of SGLTI to the transport of ACVbetaglc was not observed. NMR spectroscopic analysis indicated that the glucose conformation of ACVbeta(glc) was the 4C1 chair form, identical to beta-glucose or SGLT1-transportable beta-glucosides reported previously. Therefore, other factors such as molecular size and charge due to aglycone may cause no transport of ACVbeta(glc) by SGLT1. On the other hand, the hydrophilicity of ACVbeta(glc) was much higher than of ACV, suggesting water solubility-derived improvement of intestinal absorption of ACV.
ACVbeta(glc) is stable and absorbable, but it is not transported by SGLT1. No involvement of SGLT1 in the ACVbeta(glc) transport is not due to glucose conformation.
表征阿昔洛韦（9-[(2-羟乙氧基)甲基]鸟嘌呤，ACV）的β-葡萄糖缀合物的肠道吸收情况，并在稳定性以及通过钠/葡萄糖共转运蛋白（SGLT1）的转运方面将其与阿昔洛韦及其类似物进行比较。
使用纤维素酶酶促合成ACVβ(glc)。用大鼠外翻小肠进行肠道吸收实验。通过核磁共振光谱分析葡萄糖部分的构象。
ACVβ(glc)在黏膜侧稳定，并在小肠的所有区域转运至浆膜侧。然而，未观察到SGLT1对ACVβglc转运有显著贡献。核磁共振光谱分析表明，ACVβ(glc)的葡萄糖构象为4C1椅式构象，与先前报道的β-葡萄糖或SGLT1可转运的β-葡萄糖苷相同。因此，其他因素如苷元的分子大小和电荷可能导致ACVβ(glc)不能被SGLT1转运。另一方面，ACVβ(glc)的亲水性远高于阿昔洛韦，表明其肠道吸收因水溶性得到改善。
ACVβ(glc)稳定且可吸收，但不能被SGLT1转运。SGLT1不参与ACVβ(glc)的转运并非由于葡萄糖构象。
