Indacrinone: a uricosuric diuretic

The renal effects of a single oral dose of 20mg indacrinone [indacrinic acid; MK196 (a racemic mixture of MK296) Merck & Co] were compared with 100mg ethacrynic acid and 100mg hydrochlorothiazide in 16 healthy volunteers.

During maximal water diuresis, indacrinone increased fractional sodium excretion from 1.19 to 4.93% of glomerular filtration rate. This was similar to the increase produced by hydrochlorothiazide (to 3.16%), but less than that produced by ethacrynic acid (to 14.5%). However, ethacrynic acid produced a rapid increase in absolute sodium excretion within 60 min which was completed within 150 min, while indacrinone produced a smaller increase which was sustained for 240 min. All 3 drugs produced a similar decrease in fractional free-water clearance (indacrinone 34.8%, ethacrynic acid 27.2%, hydrochlorothiazide 26.6%) and an increase in fractional calcium clearance and absolute magnesium excretion, but no significant change in either fractional potassium or phosphate excretion. After indacrinone, fractional urate clearance increased from 6.68 to 15.20% and plasma urate decreased from 0.45 to 0.41 mM, while after ethacrynic acid and hydrochlorothiazide there was no significant change in urate clearance. During hydropenia, both indacrinone and ethacrynic acid inhibited reabsorption of solute-free water significantly by 29.3 and 73.5% respectively, but hydrochlorothiazide increased reabsorption by 29.7%. Indacrinone and ethacrynic acid both decreased urinary pH.

After 8 days' treatment with indacrinone (1Omg/ day) or hydrochlorothiazide (50 mg/day) there were significant reductions in weight and standing systolic BP, but no significant side effects. Both drugs produced similar increases in urine volume and sodium and chloride excretion but no change in potassium or phosphate excretion. Hydrochlorothiazide increased magnesium excretion, but both drugs decreased calcium excretion. Indacrinone increased fractional urate clearance significantly with no change in plasma urate, but hydrochlorothiazide increased plasma urate with no significant change in fractional urate excretion.

The evidence of inhibition of reabsorption suggests that indacrinone acts on the ascending portion of the loop of Henle, but in addition it resembles benzothiadiazines in its saluretic and antihypertensive properties, and also increases excretion of divalent cations and uric acid. Brooks, B.A. e/ al.: British Journal of Clinical Pharmacology 11: 491 (May 1984)

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