Prednisolone metabolism and excretion in the isolated perfused rat kidney.
Prednisolone metabolism and excretion in the isolated perfused rat kidney.
复制标题
泼尼松龙在离体灌注大鼠肾脏中的代谢和排泄。
DOI：
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发表时间：
1981
影响因子：
3.9
通讯作者：
W. Jusko
中科院分区：
文献类型：
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作者：
M. Rocci;S. Szefler;M. Acara;W. Jusko
采用离体大鼠肾脏灌流，研究泼尼松龙（Pn）在肾脏中消除的影响因素。Pn再循环的初始浓度从100到1000 ng/ml为90 min。灌流液和尿液样品进行分析Pn和泼尼松的HPLC。通过使用3 H-Pn和37 ℃下的平衡透析来测量Pn的蛋白结合。对照组和类固醇组的灌注液流量、肾小球滤过率、尿流量或钠排泄量无显著差异。所有研究中Pn均部分代谢为泼尼松。Pn的总肾脏清除率（CIT）范围为0.39至1.24 ml/min/100 g大鼠体重，约一半的Pn剂量无法解释为Pn或泼尼松。在尿液中以原型排泄的Pn剂量的表观百分比范围为1.9%至6.4%，与Pn剂量无关。Pn及其代谢产物泼尼松的表观尿液清除率（菊粉清除率标准化（排泄分数））是可变的，平均值分别为0.068和0.095。Pn和泼尼松的排泄分数与排出的过滤水的分数有关，但与灌流液浓度无关。因此，这些皮质类固醇的尿清除程度与肾小球滤过和被动肾小管重吸收有关。灌流的大鼠肾脏反映了Pn的尿和肾代谢清除，而没有剂量依赖性处置的并发症。
The isolated perfused rat kidney was used to identify factors responsible for the renal elimination of prednisolone (Pn). Pn was recirculated at initial concentrations varying from 100 to 1000 ng/ml for 90 min. Perfusate and urine samples were assayed for Pn and prednisone by HPLC. Protein binding of Pn was measured by using 3H-Pn and equilibrium dialysis at 37 degrees C. There were no significant differences in perfusate flow, glomerular filtration rate, urine flow, or sodium excretion between control and steroid experiments. Partial metabolism of Pn to prednisone occurred in all studies. The total kidney clearance (CIT) of Pn ranged from 0.39 to 1.24 ml/min/100 g of rat body weight with approximately half of the Pn dose unaccountable for as either Pn or prednisone. The apparent percentage of the Pn dose excreted unchanged in the urine ranged from 1.9 to 6.4% and was not related to Pn dose. The apparent urinary clearances of Pn and its metabolite, prednisone, normalized for inulin clearance (fractional excretion) were variable with means of 0.068 and 0.095, respectively. The fractional excretions of Pn and prednisone were related to the fraction of filtered water excreted but not to perfusate concentration. Thus, the extent of urinary clearance of these corticosteroids is related to glomerular filtration and passive tubular reabsorption. The perfused rat kidney reflects the urinary and renal metabolic clearance of Pn without the complication of dose-dependent disposition.