Minor S, Taylor K, Knight T F, Senekjian H O, Weinman E J
Res Commun Chem Pathol Pharmacol. 1979 Jul;25(1):53-63.
The effects of ticrynafen, a uricosuric diuretic, were examined utilizing free-flow micropuncture and clearance techniques in the rat. The intravenous infusion of ticrynafen (50 mg/kg body wt/hr) had no effect on glomerular filtration rate, but resulted in significant increases in urine flow from 4.4 +/- 0.7 microliter/min/g kidney wt to 19.2 +/- 2.6 (p less than 0.001); in urinary sodium excretion from 0.14 +/- 0.07 micronEq/min/g kidney wt to 2.35 +/- 0.52 (p less than 0.01); and in urinary urate excretion from 2.8 +/- 0.2 microgram/min/g kidney wt to 4.0 +/- 0.2 (p less than 0.005). There was no change in urinary phosphate excretion. The end-proximal TF/Pinulin ratio was 2.66 +/- 0.18 in control and 2.67 +/- 0.16 in experimental periods (p=NS). In awake animals, ticrynafen administration resulted in a decrease in CH2O from 6.47 +/- 0.12% to 3.50 +/- 0.69 (p less than 0.05), but no change in TCH2O. These studies demonstrate that ticrynafen is a uricosuric and diuretic agent in the rat. The natriuresis appears to derive from an inhibitory action of this agent in the cortical diluting segment of the nephron. In comparison to a related uricosuric diuretic, MK-196, ticrynafen is a less potent agent with respect to both its uricosuric and diuretic properties in the rat.
利用大鼠的自由流动微穿刺和清除技术，研究了尿酸排泄型利尿剂替尼酸的作用。静脉输注替尼酸（50mg/kg体重/小时）对肾小球滤过率无影响，但导致尿流量从4.4±0.7微升/分钟/克肾重显著增加至19.2±2.6（p<0.001）；尿钠排泄从0.14±0.07微当量/分钟/克肾重增加至2.35±0.52（p<0.01）；尿尿酸排泄从2.8±0.2微克/分钟/克肾重增加至4.0±0.2（p<0.005）。尿磷酸盐排泄无变化。对照期近端终末TF/P菊粉比值为2.66±0.18，实验期为2.67±0.16（p=无显著性差异）。在清醒动物中，给予替尼酸导致CH2O从6.47±0.12%降至3.50±0.69（p<0.05），但TCH2O无变化。这些研究表明，替尼酸在大鼠中是一种尿酸排泄型利尿剂。利钠作用似乎源于该药物对肾单位皮质稀释段的抑制作用。与相关的尿酸排泄型利尿剂MK-196相比，替尼酸在大鼠中的尿酸排泄和利尿特性方面效力较低。
