Itoh N, Sawada Y, Sugiyama Y, Iga T, Hanano M
Jpn J Physiol. 1985;35(2):291-9. doi: 10.2170/jjphysiol.35.291.
Extracellular reference materials are necessary to estimate tubular transport parameters for drugs which are secreted in the kidney. They must set up the flow-limited distribution between plasma and interstitial space, not be distributed to the intracellular space, and be nondegradable in the extracellular space. The capillary permeability of various molecular weight markers in the post glomerular circulation was investigated by performing pulse-injection multiple indicator dilution experiments on isolated rat kidney, using simultaneous injection of T1824-labeled albumin (the plasma reference) and creatinine (or inulin) as the extracellular reference materials. The permeability constants and the gamma values (ratio of the volume in the space of interstitium to that of capillary plasma) for creatinine and inulin were calculated by a nonlinear least squares regression. The gamma values for creatinine were greater than those for inulin, implying that the volume of distribution for creatinine is different from that for inulin. The capillary permeability clearance (CLinflux) for creatinine was 4 times higher than that of inulin, and was 3 times greater than the perfusion rate. Thus, creatinine satisfies the qualification for the flow-limited distribution between plasma and interstitial space. These findings suggest that in the rat kidney creatinine is more suitable for the extracellular reference material than inulin.
对于在肾脏中分泌的药物，细胞外参考物质对于估计肾小管转运参数是必要的。它们必须在血浆和间质空间之间建立流量限制分布，不分布到细胞内空间，并且在细胞外空间中不可降解。通过对分离的大鼠肾脏进行脉冲注射多指示剂稀释实验，同时注射T1824标记的白蛋白（血浆参考物）和肌酐（或菊粉）作为细胞外参考物质，研究了肾小球后循环中各种分子量标记物的毛细血管通透性。通过非线性最小二乘回归计算肌酐和菊粉的通透常数和γ值（间质空间与毛细血管血浆空间的体积比）。肌酐的γ值大于菊粉的γ值，这意味着肌酐的分布体积与菊粉的不同。肌酐的毛细血管通透性清除率（CLinflux）比菊粉高4倍，比灌注率大3倍。因此，肌酐满足血浆和间质空间之间流量限制分布的条件。这些发现表明，在大鼠肾脏中，肌酐比菊粉更适合作为细胞外参考物质。
