Cox P G, Moons M M, Russel F G, van Ginneken C A
Department of Pharmacology, University of Nijmegen, The Netherlands.
Pharmacology. 1991;42(5):287-96. doi: 10.1159/000138810.
We investigated renal handling and effects of indometacin on renal function in the isolated perfused rat kidney (IPK). Indometacin concentrations less than 2.5 ng/ml did not influence renal function, while higher concentrations caused a decrease in urinary flow and electrolyte excretion. The presence of 133 ng/ml prostaglandin E2 (PGE2) in the perfusate fully opposed these effects on kidney function. Only a small fraction of the filtered indometacin is excreted into the urine, indicating extensive reabsorption of the compound. This is probably a passive process, dependent on the tubular load, urinary pH and urinary flow. Indometacin accumulates extensively in the IPK, causing a kidney to perfusate ratio between 5 and 9. Accumulation decreased with increasing perfusate concentration. This can be explained by active secretion: increasing the perfusate concentration leads to a saturation of the active secretion and a decrease in the relative accumulation. We conclude that indometacin accumulates extensively in the IPK, that it affects kidney function and that this influence is probably caused by the inhibition of PGE2 synthesis.
我们研究了吲哚美辛在离体灌注大鼠肾脏（IPK）中的肾脏处理情况及其对肾功能的影响。吲哚美辛浓度低于2.5 ng/ml时不影响肾功能，而较高浓度会导致尿流量和电解质排泄减少。灌注液中存在133 ng/ml的前列腺素E2（PGE2）可完全对抗这些对肾功能的影响。滤过的吲哚美辛只有一小部分排泄到尿液中，表明该化合物有广泛的重吸收。这可能是一个被动过程，取决于肾小管负荷、尿液pH值和尿流量。吲哚美辛在IPK中大量蓄积，使肾脏与灌注液的比值在5至9之间。随着灌注液浓度的增加，蓄积量减少。这可以用主动分泌来解释：增加灌注液浓度会导致主动分泌饱和，相对蓄积量减少。我们得出结论，吲哚美辛在IPK中大量蓄积，它影响肾功能，这种影响可能是由PGE2合成的抑制引起的。
