Bumetanide and frusemide: a comparison of dose‐response curves in healthy men.

Ramsay, LE; McInnes, GT; Hettiarachchi, J.; Shelton, John; Scott, Pamela Sharkey

doi:10.1111/j.1365-2125.1978.tb01631.x

Cited by 45 publications

(22 citation statements)

References 15 publications

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“…Indacrinone is an effective diuretic in man, a single 10 mg oral dose being sufficient to almost treble the urinary loss of NaCl in the first 8 h after drug administration (Figure 2a). The approximate linearity of the dose-response curve for Na+, Cl-, and water is suggestive of 'high ceiling' diuretics (Davies, Lant, Millard, Smith, Ward & Wilson, 1974;Ramsay, McInnes, Hettiarachchi, Shelton & Scott, 1978 Table 2 The effect of a single oral dose of indacrinone (10 mg) on urinary excretion of Ca2", Mg2 + and P043 -in four subjects maintained on a metabolically controlled diet of fixed Na+, K+, Ca2 + and Mg2 + content (mmol/day: Na+ 150; K+ 80; Ca2+ 18; Mg2 + 9). Results are expressed as mean absolute excretion/period + s.e.mean (n = 4).…”

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%

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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“…Daily total calcium intake was assessed according to reported dietary intake of milk, cheese, milk products and use of calcium supplements [11]. In order to assess dose-effect relationships, doses of bumetanide were converted into furosemide dose-equivalents according to the natriuretic potency of the two diuretics, that is 1 mg of bumetanide is equivalent to approximately 40 mg of furosemide [12].…”

Section: Measurements and Biochemistrymentioning

confidence: 99%

Effects of long‐term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover

Rejnmark

Vestergaard

Heickendorff

et al. 2005

Journal of Internal Medicine

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Abstract. Rejnmark L, Vestergaard P, Heickendorff L, Andreasen F, Mosekilde L (Aarhus University Hospital and Aarhus University, Aarhus, Denmark). Effects of long-term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover. J Intern Med 2005; 257: 176-184.Background. Loop diuretics (LD) are widely used in the treatment of cardiovascular diseases and disorders with fluid accumulation. LD are known to increase renal calcium losses and may thereby affect calcium homeostasis and bone metabolism. Objective. We studied to what extent long-term treatment with LD affects calcium homeostasis and bone metabolism. Design and subjects. In a cross-sectional design we compared 140 postmenopausal women treated with a LD for more than 2 years with 140 age-matched women not in diuretic therapy. Results. Treatment with LD was associated with significantly increased urinary calcium, plasma parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D levels. Per 40 mg day )1 of furosemide,

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“…However much of the data from which this ratio was derived was based on single dose comparisons. Ramsay et al (1978) found the best estimate of natriuretic potency (bumetanide:frusemide) over a 6 h period was 46:1 in the range 0.5 mg -2 mg bumetanide. In the present study frusemide 10 mg and 100 mg were equipotent to bumetanide 0.25 mg and 2.5 mg respectively when natriuresis at individual time points were compared.…”

Section: Discussionmentioning

confidence: 93%

Comparison of the acute renal and peripheral vascular responses to frusemide and bumetanide at low and high dose.

Passmore

Whitehead

Johnston

1989

Brit J Clinical Pharma

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1 The effects of equipotent doses of frusemide (10 mg and 100 mg) and bumetanide (250 ,ug and 2.5 mg) upon renal and peripheral vascular responses, urinary prostaglandin excretion, plasma renin activity, angiotensin II and noradrenaline were compared in nine healthy volunteers. 2 Frusemide (10 mg and 100 mg) and bumetanide (2.5 mg) increased renal blood flow acutely compared with placebo but bumetanide (250 pg) had no effect. The changes in peripheral vascular responses were not significantly different from placebo. 3 Urinary prostaglandin metabolite excretion was acutely increased by all treatments, with no inter-treatment difference. Plasma renin activity was increased acutely by both doses of frusemide and by bumetanide (2.5 mg) compared with placebo and to bumetanide (250 ,ug). There were no differences between the latter two treatments. Angiotensin II was increased significantly 30 min after frusemide 100 mg and bumetanide 2.5 mg, and by all four treatments at 50 min when compared with placebo. There were no significant differences between either of the low doses or the higher doses. Plasma noradrenaline was unchanged by all treatments. 4 Frusemide 100 mg and bumetanide 2.5 mg have the same effects on the renal vasculature and the renin-angiotensin-prostaglandin system. Under the conditions of this study, frusemide 10 mg had different effects on plasma renin activity than bumetanide 250 jig.

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Bumetanide and frusemide: a comparison of dose‐response curves in healthy men.

Cited by 45 publications

References 15 publications

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

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

Effects of long‐term treatment with loop diuretics on bone mineral density, calcitropic hormones and bone turnover

Comparison of the acute renal and peripheral vascular responses to frusemide and bumetanide at low and high dose.

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