Plum Jakob, Nøhr Martha Kampp, Hansen Steen H, Holm René, Nielsen Carsten Uhd
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Biologics and Pharmaceutical Science, H. Lundbeck A/S, DK-2500 Valby, Denmark.
Int J Pharm. 2014 Oct 1;473(1-2):395-7. doi: 10.1016/j.ijpharm.2014.07.023. Epub 2014 Jul 22.
The GABA-mimetic anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro and in vivo experiments have shown that vigabatrin is transported via the proton coupled amino acid transporter (PAT1) mediating at least parts of the intestinal absorption of the drug. However, such evidence does not preclude the involvement of other transporters. The aim of the present study was, therefore, to investigate if vigabatrin interacts with taurine transport. The uptake of taurine was measured in intestinal human Caco-2 and canine MDCK cell monolayers in the absence or presence of amino acids such as GABA and vigabatrin. Vigabatrin inhibits the uptake of taurine in Caco-2 and MDCK cells to 34 ± 3 and 53 ± 2%, respectively, at a concentration of 30 mM. In Caco-2 cells the uptake of vigabatrin under neutral pH conditions is concentration-dependent and saturable with a Km-value of 27 mM (log Km is 1.43 ± 0.09). In conclusion, the present study shows that vigabatrin was able to inhibit the uptake of taurine in intestinal and renal cell culture models. Furthermore, uptake of vigabatrin in Caco-2 cells under neutral pH conditions was concentration-dependent and saturable and suggesting that vigabatrin partly was transported via a taurine transporter, which is likely to be TauT.
γ-氨基丁酸模拟物抗癫痫药物氨己烯酸用于治疗婴儿痉挛症。体外和体内实验表明，氨己烯酸通过质子偶联氨基酸转运体（PAT1）转运，该转运体至少介导了药物的部分肠道吸收。然而，这些证据并不排除其他转运体的参与。因此，本研究的目的是调查氨己烯酸是否与牛磺酸转运相互作用。在不存在或存在诸如γ-氨基丁酸和氨己烯酸等氨基酸的情况下，在人肠道Caco-2细胞单层和犬肾MDCK细胞单层中测量牛磺酸的摄取。在30 mM的浓度下，氨己烯酸分别将Caco-2细胞和MDCK细胞中牛磺酸的摄取抑制至34±3%和53±2%。在Caco-2细胞中，中性pH条件下氨己烯酸的摄取呈浓度依赖性且可饱和，Km值为27 mM（log Km为1.43±0.09）。总之，本研究表明氨己烯酸能够抑制肠道和肾细胞培养模型中牛磺酸的摄取。此外，中性pH条件下Caco-2细胞中氨己烯酸的摄取呈浓度依赖性且可饱和，这表明氨己烯酸部分通过牛磺酸转运体转运，该转运体可能是TauT。
