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At least 19 recordsLinked to original sources
PubMed1975

The supra-additive natriuretic effect addition of bendroflumethiazide and bumetanide in congestive heart failure. Permutation trial tests in patients in long-term treatment with bumetanide.

The additive natriuretic effect of a single dose of bendroflumethiazide, 5 mg., has been studied in patients with advanced congestive heart failure in long-term treatment with bumetanide, 4 mg., daily. Three permutation trial tests were performed including six patients each. In the first trial, the response to supplementary bendroflumethiazide, 5 mg., was definitely superior to that of additional bumetanide, 4 mg., in terms of renal output of sodium, chloride, potassium, water, and osmolar clearance. In the second trial, a similar pattern was found in patients receiving a combination of bumetanide, 4 mg., and spironolactone, 100 mg., daily. The third trial compared the effects of bendroflumethiazide, 5 mg., plus bumetanide, 4 mg.; of bendroflumethiazide, 5 mg.; and of bumetanide, 4 mg. In terms of natriuresis and chloruresis, the response to the combination of two drugs was significantly larger than the sum of the effects of other treatments. It is concluded that the combined effects of the drugs represent a supra-additive effect addition for sodium and chloride. A tentative explanation of the mechanism of interaction in terms of inhibition of renal tubular supplementary spironolactone, involve a tendency to development of hypokalemia, hypochloremia, and alkalosis, it is recommended that supplementary use of bendroflumethiazide in this setting is combined with the administration of potassium chloride or potassium-saving diuretics.

Adult↗
PubMed1976

Diuretic action of bumetanide in advanced chronic renal insufficiency.

The effect of bumetanide, a new potent diuretic, was studied in twelve patients with severe chronic renal failure (GFR 2.7 - 10.7 ml/min). Bumetanide 8 mg i.v. caused increased excretion of water and sodium in all patients. In some patients sodium excretion was greater than 50% of filtered load indicating an effect on proximal tubules. Bumetanide 2 mg i.v. was significantly less effective than 8 mg and a greater diuretic effect was produced by bumetanide 16 mg. In a comparative study bumetanide 8 mg was less potent than furosemide 250 mg, a finding in contrast to the potency rate ratio of 1/40 in other conditions. Side effects consisted of mild to moderate muscle pain and stiffness, especially localized in the neck, shoulders and calves. These side effects occurred only in patients with a GFR less than 5.3 ml/min. They were noted in all patients receiving 16 mg and in 3 out of 12 patients who took bumetanide 8 mg. There was no relationship between the occurrence of side effects and plasma bumetanide levels, electrolyte levels or the renal excretion of bumetanide and electrolytes.

Adult↗
PubMed1992

Pharmacokinetics and pharmacodynamics of bumetanide in neonates treated with extracorporeal membrane oxygenation.

Eleven term neonates treated with extracorporeal membrane oxygenation received bumetanide to treat volume overload. All patients had stable renal function, no history of prior diuretic therapy, and no overt evidence of hepatobiliary disease or hypoalbuminemia. Pretreatment creatinine clearance was 35.2 +/- 4.5 ml/min per 1.73 m2 (range, 20.3 to 57.5). Bumetanide, 0.095 +/- 0.003 mg/kg, was administered for 2 minutes into the postmembrane side of the extracorporeal membrane oxygenation circuit. Serial plasma and urine samples were collected for measurement of bumetanide and electrolyte concentrations. Total plasma and renal clearances for bumetanide were 0.63 +/- 0.11 and 0.16 +/- 0.04 ml/min per kilogram, respectively. The steady-state volume of distribution (0.44 +/- 0.03 L/kg) and the elimination half-life (13.2 +/- 3.8 hours) were greater than similar values reported in previous studies of bumetanide disposition in premature and term neonates who were not treated with extracorporeal membrane oxygenation. At observed rates of bumetanide excretion, the diuretic, natriuretic, and kaliuretic responses were linear. Significant diuresis, natriuresis, and kaliuresis were observed, although the duration of these effects was less than expected given the prolonged renal elimination of bumetanide. Nonrenal elimination of bumetanide was variable (47.2% to 96.9%) but higher than expected; this may explain the relatively brief diuretic and kaliuretic response.

Analysis of Variance↗
PubMed1977

Fate of [14C]-bumetanide in man.

1. The fate of bumetanide was studied in four healthy volunteers both after intravenous oral administration of [14C]-bumetanide (0.5 mg). 2. The absorption of oral [14C]-bumetanide was rapid (absorption half-life 0.61 h) and complete with a urinary recovery of about 80% of the intravenous or oral dose during 48 h. 3. The elimination of [14C]-bumetanide was rapid with a half-life of elimination (T 1/2 beta) of 1.5 h. 4. Protein bound fraction of [14C]-bumetanide in plasma was 95%. No bumetanide was found in red blood cells. 5. Four metabolites of [14C]-bumetanide were found in urine. Together they accounted for about one third of the radio-activity excreted into urine during the first 6 h after the administration of the drug. 6. Bumetanide is rapidly and completely absorbed from the gastrointestinal tract, bound extensively to plasma proteins, metabolized to some extent and excreted rapidly, principally into urine.

Adult↗
PubMed1978

Distribution of intracortical renal blood flow induced by bumetanide in the dog.

Experiments were performed in hydropenic, anesthetized dogs to investigate the effect of two dose levels of bumetanide on sodium excretion, urinary concentration, total renal blood flow and intracortical distribution of blood flow using the radioactive microsphere technique. Intravenous administration of bumetanide (0.025 mg/kg followed by 0.025 mg/min) did not alter blood flow within the kidney. A higher dose of bumetanide (0.1 mg/kg followed by 0.1 mg/min) significantly increased total renal blood flow and lowered renal vascular resistance. The rise in renal blood flow after bumetanide was due entirely to an increase in perfusion to the midcortical and juxtamedullary regions. A transient rise in plasma renin activity was measured only after the higher dose of bumetanide. Both doses of bumetanide increased sodium excretion and depressed solute free water reabsorption, although natriuresis was greater in response to the high dose. The results indicate that higher dose levels of bumetanide can increase total renal blood flow to the inner cortex. However, changes in renal blood flow were apparently not essential for the diuretic action of bumetanide because a significant natriuresis was observed in a setting where no change in intrarenal hemodynamics could be detected.

Animals↗
PubMed1976

A comparative diuretic and tissue distribution study of bumetanide and furosemide in the dog.

Intravenous dose-response data obtained from renal clearance studies in anesthetized dogs indicated that bumetanide was approximately 30-fold more potent than furosemide in enhancing sodium excretion. After the administration of 0.01 mg/kg of bumetanide or 1.0 mg/kg of furosemide, the relationship between i.v. diuretic activity and tissue distribution was evaluated. In dog renal clearance experiments, bumetanide and furosemide significantly enhanced urine flow, sodium and potassium excretion. Inulin clearance as an estimate of glomerular filtration rate was not altered by either drug, but sodium reabsorption was decreased with bumetanide (13%) and furosemide (12%). At these diuretic doses, both compounds were bound to dog plasma protein to about the same extent (86-91%), although total plasma levels were 100-fold higher for furosemide. Within 1/2 hour after the i.v. administration of 14C-bumetanide or 14C-furosemide, 86 to 99% of the 14C in urine, plasma, kidney, and liver appeared as unchanged drug. One minute after maximal diuresis bumetanide was found to have a higher affinity (3-fold) for kidney compared to furosemide. These data offer a possible explanation for the i.v. diuretic potency difference between these two compounds. Furthermore, the lack of significant difference in plasma protein binding and the absence of urinary metabolites of either drug suggest that other factors may also contribute to the marked differences in diuretic activity between bumetanide and furosemide.

Animals↗
PubMed1976

Bumetanide, a new loop diuretic.

The effect of bumetanide on renal function has been compared with that of furosemide and a placebo in a double-blind study of 9 healthy young men. The sequence for oral administration of the drug was subjected to a random assignation based upon the Latin-square methodology under three different conditions. (1) Normal hydration: The administration of bumetanide (2 mg) produced within the next 4 hr a diuresis comparable to that induced by 80 mg of furosemide. Urinary excretion of sodium, potassium, chloride, calcium, and uric acid also followed comparable patterns. Phosphaturia occurred only under bumetanide. The effect of bumetanide seemed longer lasting. (2) Water loading: The effects of bumetanide and furosemide were comparable with the exception of the phosphaturic effect induced by bumetanide. The action of both diuretics on the diluting segment of the nephron was well demonstrated by the marked depression of CH2O. (3) Water deprivation: The effects of the two diuretics were comparable, including depression tCH20. In none of these conditions did the placebo produce any significant effect.

Adult↗
PubMedDate not supplied

Comparison of bumetanide and hydrochlorothiazide on renal potassium and hydrogen ion excretion.

The purpose of this study was to compare the renal electrolyte excretion pattern of bumetanide with that of hydrochlorothiazide in dogs anesthetized with pentobarbital. In bumetanide-treated animals, mean sodium excretion rose to 12 per cent of the filtered load, while hydrochlorothiazide increased sodium excretion to 4 per cent of the filtered load. After bumetanide, urine pH fell from 6.1 to 5.1 and net hydrogenion excretion increased significantly. After hydrochlorothiazide, urinary pH went from 6.4 to 7.4, and there was no change in net hydrogen ion excretion. Potassium excretion rose to 106+/-22 muEq/min with bumetanide and to 99+/-17 muEq/min with hydrochlorothiazide. These changes in electrolyte excretion occurred despite lack of changes in arterial blood gases, arterial blood pressure, and glomerular filtration rate. In addition, bumetanide did not exert an inhibitory effect on potassium excretion under conditions of potassium loading. It is concluded that bumetanide produces a higher urinary Na+:K+ ratio with a lower pH than hydrochlorothiazide and that renal potassium ion excretion in response to sulfamoyl diuretics is not solely dependent on the rate of sodium excretion.

Animals↗
PubMed1976

Bumetanide: radioimmunoassay and pharmacokinetic profile in humans.

A simple, specific, and sensitive radioimmunoassay was developed for the determination of the diuretic bumetanide in plasma and urine. Antiserum to bumetanide was obtained from rabbits immunized with an immunogen prepared by covalently coupling the glycine conjugate of bumetanide to bovine serum albumin. Following extraction of the sample at pH 5.5 with ether, radioimmunoassay of the residue from the ether extract allows for the determination of bumetanide with a limit of sensitivity of about 1 ng/ml using 0.1 ml of plasma or urine. The specificity of the radioimmunoassay was established by comparison with specific radiometric and spectrofluorometric techniques. The pharmacokinetic profile of bumetanide in eight human subjects receiving single 2-mg oral doses of the drug was elucidated using the radioimmunoassay. The peak plasma levels ranged from 39 to 50 ng/ml at 1-4 hr after administration and declined with a mean apparent half-life of 1.17 hr. The mean plasma clearance rate was calculated to be 255 ml/min. During the first 24 hr, a mean of 43% of the bumetanide dose was excreted in the urine as intact drug.

Adult↗
PubMed1977

Effect of bumetanide and furosemide on the thick ascending limb of Henle's loop of rabbits and rats perfused in vitro.

Direct effects of bumetanide and furosemide on the thick ascending limb of Henle's loop (TALH) were compared by using the isolated tubules of rabbits and rats perfused in vitro. Both drugs, applied to the lumen, reversibly suppressed the lumen positive potential (PDt) of the rabbit TALH. Bumetanide also suppressed the PDt in the absence of Na+ where the NaCl of the artificial solutions was replaced by choline chloride. The efflux of 36Cl was also reduced by the addition of bumetanide to the perfusate. The dose-response analysis disclosed that bumetanide was 14 times as potent as furosemide. The onset and duration of bumetanide action was significantly longer than that of furosemide. Bumetanide also suppressed the PDt of the rat TALH when it was added to the perfusate.

Animals↗
PubMed1992

Novel bumetanide-sensitive K+ transport in preimplantation mouse conceptuses.

Ouabain-resistant K+ transport activity was characterized primarily by measuring Rb+ uptake because 86Rb+ has a more convenient half-life than 42K+. Ouabain-resistant 86Rb+ uptake by mouse two-cell conceptuses and blastocysts was slowed by the K(+)-Na(+)-2Cl- cotransporter inhibitors bumetanide [inhibitory constant (Ki) = 400 nM] and furosemide (Ki approximately 10 microM), but it was insensitive to a variety of K+ channel blockers. This component of 86Rb+ transport was also inhibited by K+ and nonradioactive Rb+ and it was stimulated by Cl-. Nevertheless, neither 36Cl- nor 22Na+ uptake was inhibited by bumetanide, whereas 42K+ uptake was inhibited by both bumetanide and furosemide. Bumetanide-sensitive Rb+ transport in blastocysts had a Hill coefficient of 1.0 and a Michaelis constant value of 3.0 mM. By these criteria, preimplantation conceptuses contain a novel, bumetanide-sensitive K+ transport system that does not cotransport Cl- or Na+. Moreover, bumetanide-sensitive Rb+ uptake was 10 times faster in blastocysts when they were collapsed to expose the basal membrane of the trophectoderm to 86Rb+ in the medium. Therefore, the novel system may be located predominantly in the basal rather than in the apical membrane of the trophectoderm.

Amino Acids↗
PubMed1978

Selective effects of bumetanide on chloride transport in bullfrog cornea.

Frog corneas were mounted in a modified Ussing chamber and short-circuit current (SCC) and unidirectional Cl fluxes were measured. Bumetanide, a loop diuretic, at concentrations as low as 10(-7) M, reduced the SCC 29%. At 10(-5) M, bumetanide reduced the SCC 96% and increased transcorneal electrical resistance 20-51%. The forward Cl flux declined from 0.71 +/- 0.04 to 0.20 +/- 0.03 mueq/h.cm2 (n, 7), while, in separate experiments, the backward Cl flux did not change significantly (from 0.22 +/- 0.03 to 0.23 +/- 0.04; n, 7). When corneas were mounted in Cl-free Ringer and the net Na transport was stimulated with amphotericin B, 10(-5) M bumetanide had no effect on the SCC. In separate experiments the effect of 10(-5) M bumetanide on the O2 consumption was measured in a stirrer bath assembly. Bumetanide decreased the O2 consumption from 352 +/- 14 to 297 +/- 19 microliter/h.cm2 (significantly different from sham-treated controls). This decrease was similar to that obtained with furosemide or when Cl was removed from the bathing medium. We infer from these results that bumetanide is a selective inhibitor of active Cl transport in the bullfrog cornea.

Animals↗
PubMedDate not supplied

Reduction of the endocochlear potential by the new "loop" diuretic, bumetanide.

The effect of bumetanide upon the endocochlear potential (EP) was examined in 46 guinea pigs. The EP was reduced with dosages of 5 mg/kg or more. The maximum depression of the EP (reduction to -30 to -40 mV) was obtained at a dosage of 30 mg/kg. The recovery of the potential was incomplete at any dosage within three hours and the response pattern of the EP to bumetanide was similar to that to ethacrynic acid. The present experiments revealed that bumetanide, by weight, has a stronger ototoxic potency than the other "loop" diuretics--furosemide and ethacrynic acid. However, the diuretic effect of 1 mg bumetanide is equivalent to 40 to 60 mg furosemide or ethacrynic acid. Therefore, the relative ototoxic potency of bumetanide is much smaller suggesting that from a clinical standpoint bumetanide is much safer than the other "loop" diuretics.

Action Potentials↗
PubMed1977

Diuretic effect and metabolism of bumetanide in man.

Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.

Adult↗
PubMed1978

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

1 Log dose-responses for the loop diuretics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as regards urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46:1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20:1 reported when the drugs are used at high dosage in patients with renal failure.

Adult↗
PubMed1976

The effects of bumetanide on renal function and blood composition in sheep.

Respones to bumetanide were studied in five ewes. During ADH infusion urine flow increased from less than 1-0 to approximately 11-5 cm3 min-1 within 30 min of intravenous injection of 0-02 mg kg-1 bumetanide and returned to approximately 2-0 cm3 min-1 within 3 h of dosing. The diuresis was accompanied by large increases in sodium and chloride excretion and smaller increases in potassium and free hydrogen ion excretion. Bicarbonate excretion and TCH20 were reduced. Plasma potassium and chloride concentrations decreased slightly while arterial bicarbonate pH and pCO2 slightly increased. A transient increase in GFR and RPF was followed by a small reduction in GFR. No change in CH20 was observed after bumetanide injection during water diuresis. Increasing the dose of bumetanide over the range 0-002 to 0-20 mg kg-1 resulted in more pronounced and prolonged responses. The results show that bumetanide is a potent diuretic in sheep with its main site of action on the ascending limb of Henle's loop.

Animals↗
PubMed1992

[The loop diuretic bumetanide as a tool in physiology and pharmacology].

Loop diuretics are derivatives of 4-sulfamoylbenzoic acid, which derived originally from sulfonamides. Their diuretic effect is due to the inhibition of the Na-K-Cl-cotransport system in the distal part of Henle's loop. The compounds react with different affinity with the chloride binding site of the transporter. Bumetanide is among the most potent blockers with an IC50 of 0.2 microM. The compound was developed by P. W. FEIT, 1971; the saluretic response was described first by H. H. FREY 1972. Bumetanide has outgrown to become a tool for physiologists and pharmacologists in renal transport research. The compound has essentially contributed to the elucidation of the mechanisms of volume regulation of cells. Bumetanide is taken up into tubule cells and hepatocytes by active transport. The uptake in tubule cells ist mediated by an organic anion transporter, which is involved in the renal secretion of drugs. In the liver bumetanide is transporter by the bile acid carrier. The carrier is a multispecific drug transporter, too. It is not yet known, whether both drug transport systems contain identical membrane proteins. For this purpose bumetanide is currently used to investigate by photoaffinity labeling and functional expression cloning molecular principles of the drug elimination in kidney and liver.

Animals↗