Murayama T
Hokkaido Igaku Zasshi. 1980 Nov;55(6):527-36.
Large doses of cephaloridine (CER) cause acute necrosis of the proximal renal tubule in various species, as well as gentamicin (GM). However, administration of the two drugs simultaneously resulted in a protective effect of CER against GM related nephrotoxicity in rats. The present studies were designed to examine the mechanism of CER transport system into renal cells in vitro, using the rat kidney slices and 3H-CER, effects of transport system of CER by GM or cephalexin, and effects on CO2 production in rat kidney slices of CER and GM. The results were as follows: 1. CER was transported into cells actively and intracellular concentration of CER became to be equal to extracellular concentration on around 100 mcg/ml of extracellular concentration of CER. 2. GM and CEX inhibited intracellular active transport of CER. 3. CER had inhibitory effect on CO2 production in rat kidney slices and its effect was dose dependent. GM had no effect on CO2 production. The author concluded that intracellular transport system of CER, GM and CEX is the same, and competition may be present, if each drugs are administrated simultaneously. Different attitude on CO2 production of CER and GM does not explain the difference of the mechanism of renal toxicity of each drugs directly. However, it may explain that the mechanism of renal toxicity of CER is not the same as of GM in parts.
大剂量的头孢菌素（CER）会导致多种物种的近端肾小管急性坏死，庆大霉素（GM）也是如此。然而，同时给予这两种药物会使CER对大鼠GM相关肾毒性产生保护作用。本研究旨在利用大鼠肾切片和³H-CER体外研究CER转运系统进入肾细胞的机制、GM或头孢氨苄对CER转运系统的影响以及CER和GM对大鼠肾切片二氧化碳产生的影响。结果如下：1. CER被主动转运进入细胞，当细胞外CER浓度约为100 mcg/ml时，细胞内CER浓度与细胞外浓度相等。2. GM和头孢氨苄抑制CER的细胞内主动转运。3. CER对大鼠肾切片中的二氧化碳产生有抑制作用，且其作用呈剂量依赖性。GM对二氧化碳产生无影响。作者得出结论，CER、GM和头孢氨苄的细胞内转运系统相同，如果同时给予每种药物，可能会存在竞争。CER和GM对二氧化碳产生的不同影响并不能直接解释每种药物肾毒性机制的差异。然而，这可能部分解释了CER和GM肾毒性机制的不同。
