Renal actions of a uricosuric diuretic, racemic indacrinone, in man: comparison with ethacrynic acid and hydrochlorothiazide.

Abstract

3 During hydropenia with superimposed mannitol diuresis, both IND and EA caused a fall in fractional free-water reabsorption (TCH2O/GFR x 100%), AIND = -20.3% of control, AEA = -70.1% of control. HCTZ produced a significant increase in fractional free-water reabsorption, AHCTZ = -20.7% of control. 4 In all studies, single doses of IND were both uricosuric and hypouricaemic. Fractional urate excretion increased from a mean 6.7 + 0.1 to 15.2 + 2.1% of GFR whilst plasma urate concentration fell from a mean of 0.36 + 0.03 to 0.34 + 0.03 mM (P < 0.05) within 2-3 h post drug. HCTZ and EA, in single doses, had little effect on urate excretion. 5 In the second part of the study, a total of 16 healthy volunteers received either IND, 10 mg, or HCTZ 50 mg, orally for 8 days, whilst on a diet of controlled electrolyte content. 6 Both drugs were well tolerated by both sets of subjects with no adverse clinical or pathological findings. Both IND and HCTZ caused a significant reduction in weight and standing systolic blood-pressure during the first 48 h of therapy. At the doses administered, IND and HCTZ displayed similar diuretic responses with respect to water, Na+, Cl-, Ca2+ and P04 3-excretion. IND produced less kaliuresis than HCTZ during the first treatment day but cumulative K+ loss was similar for both drugs over the eight days of therapy. 7 Fractional urate excretion after IND remained elevated throughout the 8 days of therapy and the subjects remained isouricaemic for 7 days. HCTZ caused small reductions in fractional urate excretion during the first 4 h after each daily administration: however, plasma urate concentrations remained significantly elevated throughout the study, rising from a mean pre-drug value of 0.35 + 0.01 to 0.44 + 0.01 mM (P < 0.05) after 8 days of therapy.Keywords indacrinone ethacrynic acid hydrochorothiazide diuretics 497