The effects of ticrynafen in the rat.
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.
D000042:Absorption; D000818:Animals; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006016:Glycolates / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D010642:Phenoxyacetates / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D013876:Thiophenes / Q000494:pharmacology*; D014527:Uric Acid / Q000652:urine; D014528:Uricosuric Agents / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D004232:Diuretics; D006016:Glycolates; D010642:Phenoxyacetates; D013876:Thiophenes; D014528:Uricosuric Agents; D014867:Water; D014527:Uric Acid; D011188:Potassium