Drugs Affecting the Renal Handling of Uric Acid

Fanelli, George M.

doi:10.1007/978-1-4615-8891-7_9

Cited by 11 publications

(1 citation statement)

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“…Like indacrinone, the effect of tienilic acid on urate excretion has been ascribed to inhibition of both tubular secretion and reabsorption (Prasad, Weiner & Steele, 1977) although there are considerable species variations in response ranging from increased to decreased excretion of urate (Lemieux et al, 1977). Species variability is also present with indacrinone (Zacchei & Wishousky, 1976), and may be partly explained by differences in the relative proportions of reabsorptive to secretory processes involved in the bidirectional transport of urate across the renal tubule in different animals (Fanelli, 1976). Existence of such speciesspecific patterns of renal action amongst phenoxyacetic acid analogues emphasizes the need for ascertaining pharmacological effects in man before assigning particular drug mechanisms or sites of action within the human kidney.…”

Section: Single Dose Metabolic Studymentioning

confidence: 99%

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

Brooks¹,

Blair²,

Finch³

et al. 1980

Brit J Clinical Pharma

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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.

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Section: Single Dose Metabolic Studymentioning

confidence: 99%