Kikuchi Akihiro, Nozawa Takashi, Wakasawa Takeru, Maeda Tomoji, Tamai Ikumi
Faculty of Pharmaceutical Sciences, Tokyo University of Science (RIKADAI), Noda, Chiba, Japan.
Drug Metab Pharmacokinet. 2006 Aug;21(4):308-14. doi: 10.2133/dmpk.21.308.
Both influx and efflux transporters are thought to be involved in the intestinal absorption of fexofenadine. The present study examined the influx transporter-mediated intestinal absorption of fexofenadine in rats, focusing on the role of rat oatp3 (Oatp1a5). The intestinal permeability of fexofenadine was evaluated by means of the Ussing chamber method in the presence of a P-glycoprotein inhibitor to block efflux transport. The permeability of fexofenadine from the mucosal to the serosal side was higher than that from the serosal side to the mucosal side. Transport of fexofenadine was saturable, and was significantly decreased by an organic anion transporting polypeptide (oatp) inhibitor. Furthermore, uptake of fexofenadine by Xenopus oocytes expressing rat oatp3 was significantly greater than that by water-injected oocytes, and the affinity of oatp3 for fexofenadine (Km) was about 60 microM, which is comparable with the value obtained by the Ussing chamber method using rat intestinal tissues. These results indicate that oatp3 plays a role as an influx transporter in the intestinal absorption of fexofenadine in rats.
内流和外流转运体都被认为参与了非索非那定的肠道吸收过程。本研究检测了大鼠中内流转运体介导的非索非那定肠道吸收情况，重点关注大鼠燕麦肽3（Oatp1a5）的作用。在存在P-糖蛋白抑制剂以阻断外流转运的情况下，采用尤斯灌流小室法评估非索非那定的肠道通透性。非索非那定从黏膜侧到浆膜侧的通透性高于从浆膜侧到黏膜侧的通透性。非索非那定的转运具有饱和性，并且被有机阴离子转运多肽（oatp）抑制剂显著降低。此外，表达大鼠燕麦肽3的非洲爪蟾卵母细胞对非索非那定的摄取明显高于注射水的卵母细胞，燕麦肽3对非索非那定的亲和力（Km）约为60微摩尔，这与使用大鼠肠道组织通过尤斯灌流小室法获得的值相当。这些结果表明，燕麦肽3在大鼠非索非那定的肠道吸收中作为内流转运体发挥作用。
