Studies on the mechanism and characteristics of action of a uricosuric diuretic, indacrinone (MK-196)

Br J Clin Pharmacol. 1980 Sep;10(3):249-58. doi: 10.1111/j.1365-2125.1980.tb01752.x.

Abstract

1 The renal action of indacrinone (MK-196), a phenoxyacetic acid derivative with diuretic and uricosuric properties, has been studied in fifteen male subjects. 2 Increasing single doses of up to 60 mg of oral indacrinone produced a linear increase in urinary volume and excretion of Na+ and Cl-, whilst the responses of urinary K+, Ca2+, Mg2+ and uric acid excretion, rose to a plateau at the 40 mg dose. 3 Indacrinone evoked a rapid diuretic response which reached a maximum of 2-4 h and was largely complete at 8-12 h after administration. 4 During maximal hydration, indacrinone produced a substantial fall in fractional free water clearance (CH2O), from 8.89% to 5.83% of the filtered load of water, associated with an increase in osmolal clearance, from 1.38% to 5.78% of the filtered load of solute. The reduction in CH2O was of the same order as that produced by a dose of ethacrynic acid with comparable saluretic activity and significantly greater than that produced by an equi-saluretic dose of hydrochlorothiazide. These findings imply an action of indacrinone upon solute transport in the diluting segments of the distal tubule. 5 At the time of maximal indacrinone-induced saluresis, which amounted to an increase from 0.48% to 4.61% of the filtered load of NaCl, fractional urate clearance increased from 5.16% to 12.24% of the filtered load of uric acid. 6 Indacrinone is a long acting diuretic, sharing some properties in common with both loop diuretics and benzothiadiazines. The results are discussed in relation to structure-activity amongst derivatives of phenoxyacetic acid.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Diuresis / drug effects
  • Diuretics / pharmacology*
  • Dose-Response Relationship, Drug
  • Electrolytes / urine
  • Humans
  • Indans / pharmacology*
  • Indenes / pharmacology*
  • Male
  • Urea / metabolism
  • Uric Acid / metabolism
  • Uricosuric Agents / pharmacology*

Substances

  • Diuretics
  • Electrolytes
  • Indans
  • Indenes
  • Uricosuric Agents
  • Uric Acid
  • Urea
  • indacrinone