Darling I M, Morris M E
Department of Pharmaceutics, School of Pharmacy, State University of New York, Buffalo, Amherst 14260.
Pharm Res. 1991 Mar;8(3):376-9. doi: 10.1023/a:1015805918168.
Homeostasis of inorganic sulfate is maintained by the capacity-limited renal reabsorption of sulfate in the proximal tubule. The purpose of the present investigation was to determine if probenecid, the classical inhibitor of renal organic anion secretion, may affect sulfate renal clearance. Two groups of rats were administered in a randomized crossover design, an i.v. bolus dose (20.6 or 92.4 mg/kg) and 4-hr infusion (0.28 or 0.59 mg/min/kg) of probenecid or vehicle, and blood and urine samples were collected. At a steady-state serum concentration of 0.45 mM, probenecid had no significant effect on the serum concentrations or renal clearance of inorganic sulfate, whereas at a serum concentration of 1.4 mM, probenecid treatment caused a significant decrease in serum sulfate concentrations (0.57 +/- 0.11 vs 0.96 +/- 0.19 mM in controls, mean +/- SD, n = 6, P less than 0.001) due to an increase in the renal clearance of sulfate (3.88 +/- 1.18 vs 2.13 +/- 0.84 ml/min/kg in controls, P less than 0.01). The fraction of the filtered sulfate that was reabsorbed was significantly decreased (0.38 +/- 0.23, vs 0.74 +/- 0.09 in controls, P less than 0.01). Therefore, probenecid treatment results in the inhibition of the renal reabsorption of inorganic sulfate in rats in vivo.
无机硫酸盐的稳态通过近端小管中容量有限的硫酸盐肾重吸收来维持。本研究的目的是确定经典的肾有机阴离子分泌抑制剂丙磺舒是否会影响硫酸盐的肾清除率。两组大鼠采用随机交叉设计，静脉注射大剂量（20.6或92.4mg/kg）丙磺舒或赋形剂，并进行4小时输注（0.28或0.59mg/min/kg），同时采集血样和尿样。在稳态血清浓度为0.45mM时，丙磺舒对无机硫酸盐的血清浓度或肾清除率无显著影响；而在血清浓度为1.4mM时，丙磺舒治疗导致血清硫酸盐浓度显著降低（对照组为0.96±0.19mM，丙磺舒治疗组为0.57±0.11mM，平均值±标准差，n = 6，P<0.001），原因是硫酸盐的肾清除率增加（对照组为2.13±0.84ml/min/kg，丙磺舒治疗组为3.88±1.18ml/min/kg，P<0.01）。重吸收的滤过硫酸盐部分显著降低（对照组为0.74±0.09，丙磺舒治疗组为0.38±0.23，P<0.01）。因此，丙磺舒治疗可导致体内大鼠无机硫酸盐的肾重吸收受到抑制。
