Renal secretion of [35-S]furosemide and depression by albumin binding.
Renal secretion of [35-S]furosemide and depression by albumin binding.
复制标题
[35-S]呋塞米的肾分泌和白蛋白结合抑制。
DOI：
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发表时间：
1975
影响因子：
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通讯作者：
R. H. Bowman
中科院分区：
文献类型：
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作者：
R. H. Bowman
用[35-S]速尿和超滤法测定速尿与牛血清白蛋白广泛结合。当使用500微米速尿和浓度为2.5g/100毫升的白蛋白时，大约90%的药物被结合。用同样的速尿，但用3倍的白蛋白，结合率约为98%。用浓度为25倍的速尿，20微米，与2.5g白蛋白/100ml的结合率接近98%，与7.5g/100ml的白蛋白结合率达98%以上，并用相同浓度的速尿和白蛋白考察了[35-S]速尿在大鼠肾脏的排泄和分泌。[35-S]速尿的肾小管清除率(即分泌量)与灌流液中白蛋白浓度呈负相关。在无白蛋白灌流的肾脏中，药物的肾小管清除率分别为2.5和7.5g白蛋白/100ml时的6-20倍。丙磺舒，无论有没有白蛋白，都将速尿的清除量降低到其滤过率的水平。结论是，在生理白蛋白浓度下，一小部分循环中的速尿可用于滤过，而肾小管液和尿速尿将主要来自分泌物。由于速尿与白蛋白的广泛结合，肾脏分泌过程本身受到抑制，分泌速度将部分依赖于未结合药物的浓度。
It was determined by use of [35-S]furosemide and an ultrafiltration procedure that furosemide is bound extensively to bovine serum albumin. When 500 muM furosemide and albumin at a concentration of 2.5 g/100 ml were used, approximately 90% of the drug was bound. With this same amount of furosemide, but with 3 times as much albumin, binding was about 98%. Using a 25-fold lower concentration of furosemide, 20 muM, binding was nearly 98% with 2.5 g albumin/100 ml, and was over 98% with 7.5 g albumin/100 ml. These same concentrations of furosemide and albumin were used to investigate the excretory and secretory rates of [35-S]furosemide in the isolated perfused rat kidney. Tubular clearance (i.e., secretion) of [35-S]furosemide was inversely related to the concentration of albumin in the perfusate. In kidneys perfused without albumin, tubular clearance of the drug was 6-20 times that found when 2.5 or 7.5 g albumin/100 ml, respectively, was used. Probenecid, with or without albumin, reduced the clearance of furosemide to that of its filtration rate. It is concluded that at physiological albumin concentrations, a very small fraction of circulating furosemide will be available for filtration, and tubular-fluid and urinary furosemide will arise predominantly from secretion. Because of extensive binding of furosemide to albumin, the renal secretory process itself is depressed, and the rate of secretion will be dependent, in part, on the concentration of unbound drug.