Intestinal absorption of acyclovir beta-glucoside: Comparative study with acyclovir, guanosine, and kinetin beta-glucoside

Purpose. To characterize the intestinal absorption of a beta-glucose conjug ate of acyclovir (9-[(2-hydroxyethoxy) methyl] guanine, ACV) and compare it to ACV and its analogues in terms of stability and transport by Na+/glucos e cotransporter (SGLT1). Methods. ACV beta glc was enzymatically synthesized using cellulase. Intest inal absorption experiments were performed with rat everted small intestine . Conformation of the glucose moiety was analyzed by NMR spectroscopy. Results. The ACV beta glc was stable on the mucosal side, and was transport ed to the serosal side in all regions of the small intestine. However, sign ificant contribution of SGLT1 to the transport of ACV beta glc was not obse rved. NMR spectroscopic analysis indicated that the glucose conformation of ACV beta glc was the C-4(1) chair form, identical to beta-glucose or SGLT1 -transportable beta-glucosides reported previously. Therefore, other factor s such as molecular size and charge due to aglycone may cause no transport of ACV beta glc by SGLT1. On the other hand, the hydrophilicity of ACV beta glc was much higher than of ACV, suggesting water solubility-derived impro vement of intestinal absorption of ACV. Conclusions. ACV beta glc is stable and absorbable, but it is not transport ed by SGLT1. No involvement of SGLT1 in the ACV beta glc transport is not d ue to glucose conformation.