Sugita O, Sawada Y, Sugiyama Y, Iga T, Hanano M
J Pharm Sci. 1984 May;73(5):631-4. doi: 10.1002/jps.2600730513.
The effect of sulfaphenazole on the distribution of tolbutamide was examined by comparing the change in the steady-state volume of distribution (Vdss) determined from in vivo plasma elimination with the tissue-to-plasma concentration ratio of various tissues (Kp) in rabbits; this effect was compared with that previously reported in rats. In rabbits, the Kp values of six tissues studied (i.e., brain, heart, spleen, small intestine, muscle, and skin) increased in the presence of sulfaphenazole ; except for brain, lung, and adipose tissue, the tissue-to-plasma unbound concentration ratio (Kp,f) of other tissues did show a significant decrease. This suggested that both the tissue and plasma protein binding of tolbutamide were affected by sulfaphenazole and that the increase in Kp was due mainly to the displacement of plasma protein binding of tolbutamide by sulfaphenazole , which was greater than that of tissue binding, while no change in Kp was due to a parallel change in both the plasma protein binding and tissue binding of tolbutamide. In both rabbits and rats, the Vdss calculated from plasma concentration versus time curve was very close to that calculated from the Kp values and volumes of various tissues in the presence and absence of sulfaphenazole , respectively. The interspecies difference of the effect of sulfaphenazole on the tissue distribution of tolbutamide between rabbits and rats was elucidated from both in vivo tissue distribution and in vitro plasma protein binding studies.
通过比较从体内血浆消除测定的稳态分布容积（Vdss）的变化与兔各种组织的组织与血浆浓度比（Kp），研究了磺胺苯吡唑对甲苯磺丁脲分布的影响；并将此效应与先前在大鼠中报道的效应进行比较。在兔中，所研究的六种组织（即脑、心脏、脾脏、小肠、肌肉和皮肤）的Kp值在磺胺苯吡唑存在时升高；除脑、肺和脂肪组织外，其他组织的组织与血浆未结合浓度比（Kp,f）确实显著降低。这表明甲苯磺丁脲的组织和血浆蛋白结合均受磺胺苯吡唑影响，且Kp升高主要是由于磺胺苯吡唑取代甲苯磺丁脲的血浆蛋白结合，其作用大于组织结合，而Kp无变化是由于甲苯磺丁脲的血浆蛋白结合和组织结合同时发生平行变化。在兔和大鼠中，根据血浆浓度与时间曲线计算的Vdss分别与在有和无磺胺苯吡唑情况下根据Kp值和各种组织体积计算的Vdss非常接近。通过体内组织分布和体外血浆蛋白结合研究，阐明了磺胺苯吡唑对甲苯磺丁脲组织分布影响在兔和大鼠之间的种间差异。
