Benincosa L J, Morris M E
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst.
Prostaglandins Leukot Essent Fatty Acids. 1993 Jul;49(1):503-8. doi: 10.1016/0952-3278(93)90038-x.
The objectives of the current investigation were: (1) to examine the effects of the nonsteroidal anti-inflammatory drug, tiaprofenic acid (TA), on sulfate renal reabsorption, and (2) to determine if concomitant prostaglandin E2 (PGE2) could reverse these effects. In crossover studies, female Lewis rats (n = 9) received either TA (as an intravenous (i.v.) bolus injection of 15 mg/kg and constant infusion of 0.02 mg/min) or its vehicle for 6 h. A blood sample was obtained at 5 h and urine was collected between 4 and 6 h. At a steady-state TA serum concentration of approximately 190 micrograms/ml, the PGE2 urinary excretion rate was inhibited by > 90% with no change in glomerular filtration rate (GFR), as measured by creatinine clearance. TA administration resulted in a significant decrease in serum sulfate concentrations (0.65 +/- 0.22 vs 1.1 +/- 0.15 mM, mean +/- SD, p < 0.01) and increase in sulfate clearance ratio (0.32 +/- 0.14 vs 0.13 +/- 0.06, p < 0.01) when compared to the vehicle-treated period. There was also a significant decrease in the fraction of sulfate reabsorbed by the kidneys (0.68 +/- 0.14 vs 0.87 +/- 0.06 in the vehicle-treated period, p < 0.01). In a second crossover study, rats received either TA or TA plus PGE2. PGE2 was administered as an infusion (0.1 micrograms/min) beginning 210 min after the start of the TA infusion. An additional group of rats served as controls and received both vehicles.(ABSTRACT TRUNCATED AT 250 WORDS)
(1)研究非甾体抗炎药噻洛芬酸(TA)对肾脏硫酸盐重吸收的影响,(2)确定同时给予前列腺素E2(PGE2)是否能逆转这些影响。在交叉研究中,雌性Lewis大鼠(n = 9)接受TA(静脉推注15 mg/kg,持续输注0.02 mg/min)或其溶媒,持续6小时。在5小时时采集血样,并在4至6小时收集尿液。在TA血清稳态浓度约为190微克/毫升时,PGE2尿排泄率被抑制> 90%,而肌酐清除率测定的肾小球滤过率(GFR)无变化。与给予溶媒的时期相比,给予TA导致血清硫酸盐浓度显著降低(0.65 +/- 0.22对1.1 +/- 0.15 mM,均值 +/- 标准差,p < 0.01),硫酸盐清除率比值增加(0.32 +/- 0.14对0.13 +/- 0.06,p < 0.01)。肾脏重吸收的硫酸盐比例也显著降低(溶媒处理期为0.87 +/- 0.06,给予TA期为0.68 +/- 0.14,p < 0.01)。在第二项交叉研究中,大鼠接受TA或TA加PGE2。PGE2在TA输注开始210分钟后开始输注(0.1微克/分钟)。另一组大鼠作为对照,接受两种溶媒。(摘要截断于250字) )