Yoshikawa T, Muranushi N, Yoshida M, Oguma T, Hirano K, Yamada H
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Pharm Res. 1989 Apr;6(4):302-7. doi: 10.1023/a:1015994323639.
The transport characteristics of ceftibuten in rat intestinal brush-border membrane vesicles were investigated by a rapid filtration technique. Ceftibuten uptake was markedly stimulated by an inwardly directed H+ gradient (pH 7.5 inside, pH 5.5 outside) in comparison with that in the absence of a H+ gradient. The uptake at 30 sec was four times greater than that observed at equilibrium (overshoot phenomenon), while the H+ gradient-stimulated uptake of ceftibuten was markedly reduced in the presence of FCCP, a protonophore. These results suggested H+-coupled uphill transport of ceftibuten. In contrast, an inwardly directed Na+ gradient had no effect on ceftibuten uptake. The valinomycin-induced K+ diffusion potential (inside positive) significantly stimulated the ceftibuten uptake, suggesting net transfer of the negative charge. In contrast to the cis-isomer ceftibuten, the trans isomer of ceftibuten is not readily absorbed from the intestine, and its uptake was found not to be affected by a H+ gradient. Since the lipophilicity of the trans isomer is similar to that of ceftibuten, the uptake process appears to be stereoselective. The initial uptake of ceftibuten and its analogue cefaclor was concentration dependent under a H+ gradient. The apparent Km value was 0.2 mM for ceftibuten and 3.0 mM for cefaclor.
采用快速过滤技术研究了头孢布烯在大鼠小肠刷状缘膜囊泡中的转运特性。与不存在H⁺梯度时相比，内向性H⁺梯度（内部pH 7.5，外部pH 5.5）显著刺激了头孢布烯的摄取。30秒时的摄取量比平衡时观察到的摄取量大四倍（过冲现象），而在质子载体FCCP存在的情况下，H⁺梯度刺激的头孢布烯摄取量显著降低。这些结果表明头孢布烯存在H⁺偶联的上坡转运。相比之下，内向性Na⁺梯度对头孢布烯的摄取没有影响。缬氨霉素诱导的K⁺扩散电位（内部为正）显著刺激了头孢布烯的摄取，表明有负电荷的净转移。与顺式异构体头孢布烯不同，头孢布烯的反式异构体不易从肠道吸收，并且发现其摄取不受H⁺梯度的影响。由于反式异构体的亲脂性与头孢布烯相似，摄取过程似乎具有立体选择性。在H⁺梯度下，头孢布烯及其类似物头孢克洛的初始摄取呈浓度依赖性。头孢布烯的表观Km值为0.2 mM，头孢克洛的表观Km值为3.0 mM。
