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PubMed1979

[Acute effects of bumetanide in healthy subjects. A comparative study with furosemide (author's transl)].

A comparative test on the efficacy of bumetanide and furosemide was made in ten healthy individuals. The effect on diuresis and urinary excretion of ions and metabolites after the acute oral administration of 1 mg bumetanide and 40 mg furosemide was observed. From the results of the experiment it can be concluded that the effectiveness of bumetanide is about 15 percent superior to that of furosemide with a later but more sustained effect. The excretion of Na and K was similar with both compounds but the chloruresis was more intense with furosemide. Although the excretion of uric acid was increased too, it was proportionally less than the increase of the diuresis obtained with both drugs. A noticeable increase of the urinary excretion of calcium caused by bumetanide stands out. The authors suggest its possible therapeutic usefulness in patients with hypercalcemia as well as its possible mechanism of action on the reabsorption of calcium. In every case tolerance of both drugs was good and there were no signs of toxicity or adverse side effects. Generally speaking the doses of 1 mg bumetanide and 40 mg furosemide were judged to be equally powerful.

Administration, Oral↗
PubMed1985

Effect of furosemide upon extracellular fluid volume depletion and kidney denervation in rats.

The effect of the diuretic Furosemide (4 mg/kg) is tested on rats housed in metabolic, cages. The excretory function of the kidneys is studied over a 2-hour period after Furosemide administration, according to the following parameters: diuresis, glomerular filtration, excretion and excretory functions of sodium, potassium, chlorine and total osmotically active substances. Reduction of the volume of the extracellular fluid (ECF) is induced by intraperitoneal administration of 0.3 M glucose solution in amount equal to 10 per cent of the body mass. Comparative studies are carried out in animals with intact kidneys (IK) and with bilaterally denervated kidneys (DK). The decreased ECF volume is found to limit strongly the diuretic and saliuretic effect of Furosemide. In the experimental animals with DK, the reduced ECF volume reduced the diuretic and saliuretic effect of Furosemide to a considerably lesser extent. In euvolemic animals Furosemide has potentiated effect in the case of DK. The conclusion reached is that intact kidney innervation is necessary for the Na-retaining function of the kidneys in the case of depleted ECF volume.

Aldosterone↗
PubMed1985

Comparative bio-availability of four formulations of furosemide.

Twelve healthy white male volunteers participated in a randomized double-blind cross-over study to compare the bio-availability of four brands of furosemide marketed in the RSA. A 40 mg tablet of each of the following formulations, purchased at random, was administered: Aquasin; Furetic; Lasix; and Puresis. Blood specimens were taken up to 5 hours and urine specimens collected up to 6 hours after medication. The following parameters were used to compare the formulations: (i) area under the plasma concentration time curve (AUC); (ii) maximal plasma concentration of furosemide (Cmax); (iii) time to maximal furosemide plasma concentration; (iv) cumulative urine volumes; and (v) cumulative excretion of furosemide in urine. Lasix was significantly superior to the other three products in respect of AUC and Cmax. With regard to cumulative urine volumes Lasix was significantly (P less than 0,05) superior to Aquasin in the first 3 hours after medication, significantly superior (P less than 0,05) to Puresis and comparable to Furetic over the entire 6-hour collection period. Lasix resulted in a significantly greater cumulative urinary excretion of furosemide than Puresis and Aquasin over the entire collection period. Lasix was superior to Furetic at 6 hours after medication. It is concluded that the bio-availability of Lasix is superior to that of the other products tested.

Adolescent↗
PubMed1985

Dynamics of renal excretory function after furosemide or ethacrynic acid administration to unanaesthetized dogs after mannitol infusion or chronic renal denervation.

To unanesthetized dogs with exteriorized ureter allowing separate collection of urine from both kidneys, furosemide 0.2 mg/kg b.w. or ethacrynic acid 0.22 mg/kg b.w. was given intravenously. The volume of collected urine and the excretion of sodium, chloride, potassium and calcium were studied. The dynamics of diuretic administration was programmed. After unilateral renal denervation furosemide or ethacrynic acid was given and the response of the denervated (left) and intact (right) kidneys was compared. Prior to renal denervation the same dogs were infused with a 15% mannitol solution in a quantity and at a rate causing an increase of diuresis approximately equal to that after renal denervation. The effect of furosemide given with and without mannitol infusion was compared. Description of the dynamics of renal excretory function used by us allowed to demonstrate the modulating role of renal nerves in the regulation of water, chloride and sodium excretion after the administration of diuretics. The principal part of the compensatory reabsorption of chloride after renal denervation occurred in the ascending limb of Henle's loop. Comparison of calcium excretion after renal denervation and administration of furosemide with that after mannitol and furosemide allows to assume that after renal denervation calcium load from the proximal to the distal tubules does not increase.

Animals↗
PubMed1985

Pharmacokinetics and pharmacodynamic effects of furosemide in patients with liver cirrhosis.

Ten patients with compensated cirrhosis of the liver, 7 patients with portal decompensated cirrhosis of the liver and 10 patients with intact liver function were investigated. After intravenous injection of 40 mg furosemide elimination half-life, total and excretory clearance were not significantly different in the 3 groups investigated, but renal clearance was enhanced in the 2 cirrhosis groups and nonrenal clearance diminished in patients with decompensated cirrhosis of the liver. In those patients distributional volumes were significantly higher than in the control group. According to the increased urinary excretion of unchanged furosemide in patients with cirrhosis of the liver, the pharmacodynamic effect of the drug is enhanced: In the first 4-h-collecting period the excretion of water, chloride and sodium is significantly more increased than in the control group. After a period of 24 h this effect is still noticeable. The effect of furosemide on the excretion of potassium, creatinine and urea nitrogen is not significantly influenced by liver disease. Doubling the dose from 40 to 80 mg furosemide did not enhance the diuretic effect of the drug despite the doubled urinary excretion of unchanged furosemide.

Adult↗
PubMed1985

Protein binding studies of furosemide and penbutolol.

Serum protein binding of furosemide and penbutolol, the active principles of Betasemid (Hoe 9358), was studied by equilibrium dialysis. Membranes from commercial dialysis tubes were used within commercially available cells. Serum drug and portion unbound in buffer were determined by quantitative thin-layer chromatography. In the range of 1-20 micrograms drug/ml serum, 96 +/- 0.3% of furosemide vs. 88 +/- 4% of penbutolol were bound to proteins. The same results were obtained, when the two substances simultaneously interacted with proteins. Thus, specific protein binding sites for both compounds were demonstrated. For both drugs, Scatchard plots revealed two classes of specific binding sites with statistical mean values/protein of 0.4 and 5 in the case of furosemide and 0.04 and 0.3 in the case of penbutolol. Binding energies were 27.6 and 19.6 kJ/mol furosemide vs. 31.5 and 23.9 kJ/mol penbutolol. Further, serum protein binding of furosemide was studied by ultrafiltration. A micropartition system MPS-1 was used. Results were the same as those from equilibrium dialysis.

Blood Proteins↗
PubMed1985

Effect of furosemide on urinary excretion of 4-hydroxy-3-methoxymandelic acid (VMA).

Excretion of VMA was measured in 10 healthy volunteers before and after intake of 40 mg furosemide and in 3 patients with congestive heart failure who were intermittently treated with 80 mg furosemide. In healthy volunteers furosemide caused an increase in VMA excretion from 5.0 +/- 0.5 to 7.8 +/- 0.9 mg/24 h and from 2.0 +/- 0.2 to 2.9 +/- 0.3 mg/g creatinine (mean +/- SE). Excretion of catecholamines was slightly increased in some subjects, but did not reach the upper limit of normal in any case. Furosemide induced an acute increase in urinary VMA that could have derived from inhibition of renal tubular reabsorption. Administration of furosemide might result, on occasion, in a false positive test for pheochromocytoma.

Catecholamines↗
PubMed1979

Effect of furosemide on peripheral venous compliance following ureteral ligation in the adult dog.

The effect of furosemide on peripheral venous compliance in the absence of the diuretic effect of the drug was examined. Following bilateral ligation of the ureters, adult dogs were given furosemide, 2 mg/kg. A significant increase in peripheral venous compliance was observed as early as ten minutes after the drug was given (120% of control), and an additional increase was seen at 60 minutes after administration of the drug (136% of control). No change in peripheral venous compliance was observed in animals receiving only the furosemide vehicle, nor was there any change in animals in which bilateral nephrectomy had been performed prior to the administration of furosemide. These results indicate that furosemide produces a significant increase in peripheral venous compliance, which is independent of its diuretic action. However, the presence of the kidneys appears to be necessary for this effect.

Animals↗
PubMed1979

Use of furosemide to obtain bovine urine samples for leptospiral isolation.

The use of the diuretic furosemide made it possible to obtain samples of urine from cattle for leptospiral isolations. The drug was injected IV at a dose level of 0.8 mg/kg for heifers and 0.5 mg/kg for calves. The average time to first voiding in heifers was 19 minutes. The average time from the first to the second voiding was 17 minutes. The average time to the first voiding in four calves was 12 minutes; the average time from the first to the second voiding was 10 minutes. A decrease in urinary osmolarity provoked by furosemide created a more favorable condition for the survival of leptospires. Leptospires were isolated in 24 (72.7%) of 33 weekly cultural attempts with the aid of furosemide in three experimentally infected adult cattle. Serovar hardjo was isolated in 16 (57.1%) of 28 weekly cultural attempts with aid of the diuretic in four experimentally infected calves. The recovery frequency was 28.5% from the first voiding and 50% from the second. Leptospires were not isolated from urine obtained from the calves by manual stimulation. Untoward side effects that might have been attributable to furosemide were not observed. Furosemide appears to be well suited to obtain urine samples from cattle for leptospiral isolation.

Animals↗
PubMed1978

[Effect of furosemide on the hemodynamics of the kidney medulla during salt depletion].

UNLABELLED: In sodium depleted rats cortical and medullary blood flow was studied before and after 4-chloro-N-(2-furylmethyl)-5-sulfamoyl-anthranilic acid (furosemide). 86Rb was used as an indicator of renal hemodynamics. Its activity was assessed in systemic blood and in tissue slices of the kidney. At the beginning of the experiments the animals were loaded p.o. with 1.3 ml/100 g b.w. of isotonic saline. 3 h later a rapid i.v. injection of 50 muCi (=5.6 MBq) 86Rb was given to 12 control and 9 furosemide treated animals. RESULTS: After 0.7 mg/100 g b.w. of furosemide the sodium and water excretion rises to 820% and 860% resp. (p less than 0.0005). Systemic body hematocrit increases from 47 to 49%. The renal cortical blood flow is not influenced by furosemide. Compared with controls there is a decrease in blood flow through the outer medulla from 1.57 +/- 0.65 to 1.00 +/- 0.37 ml/g.min, through the inner medulla from 0.75 +/- 0.30 to 0.59 +/- 0.23 ml/g.min, and through the papillary tips from 0.85 +/- 0.40 to 0.46 +/- 0.18 ml/g.min. However, these hemodynamics changes are not significant. It is concluded that the decrease in renal medullary hemodynamics of furosemide-treated rats is due to a stimulation of the renin-angiotensin system.

Animals↗
PubMed1977

[Change in plasma renin activity in patients with hypertension and healthy persons after furosemide intake].

Blood plasma renin activity was studied by the radioimmune method in clino- and orthostatism in 36 males with hypertensive disease and in 15 healthy males before and after 3-day medication with furosemide in a daily dose of 120 mg under in-patient conditions. Renin activity proved to be higher in double stimulation (in orthostatism after furosemide intake) than in orthostatism before the intake of the drug. Diversity was revealed between patients with different stages of hypertensive disease. Stage IB of the disease was characterized by increased renin activity in orthostatism and marked reaction to stimulation with furosemide. In stage IIB, on the contrary, renin activity was low and the reaction to stimulation with furosemide weak. Hypotensive effect after intake of furosemide was observed in patients with IIB stage of hypertensive disease.

Adolescent↗
PubMed1978

[Effects of furosemide on hemodynamic, electrocardiographic, and symptomatic responses to exercise in patients with angina pectoris (author's transl)].

In 12 patients with coronary artery disease and typical exercise-induced angina pectoris hemodynamic and ECG studies were performed at rest and during ergometer load in supine position. During the attacks of angina there was a significant ST-depression in all cases accompanied by elevated pulmonary capillary wedge pressures (PCP) and pulmonary artery mean pressures (PAM). Intravenous administration of 40 mg furosemide showed consistent hemodynamic changes. Cardiac output (CO) dropped significantly by 15.9 per cent at rest (p is less than 0.001) and by 6.9 per cent during exercise (p is less than 0.005). The PCP during exercise following furosemide decreased from 32.9 mmHg to 11.8 mm Hg (p is less than 0.001) and was paralleled by a significant decrease of PAM, indicating reduction of ischemia-related hemodynamic impairment. Furthermore, there was a striking improvement of Ecg findings during ergometer load in 9 of 12 patients as well as a relief of anginal pain in 11 of 12 patients. The present demonstration of antianginal properties of furosemide may be explained by the reduction of ventricular volumes and pressures, resulting in a decrease of myocardial wall stress. These effects are suggested to be related to the peripheral venodilator capacity of furosemide in conjunction with its diuretic properties. Thus, in patients with left ventricular dysfunction secondary to ischemia, intravenous furosemide may have salutary effects on myocardial oxygen requirements resembling the action of nitroglycerin, but without its oxygen-wasting effects on tachycardia.

Adult↗
PubMed1984

Long-term furosemide treatment in idiopathic edema.

Of 12 patients with idiopathic edema, ten patients had received total doses of furosemide of up to about 950 g. A good negative correlation was observed between the creatinine clearance and the duration of daily oral furosemide intake of more than 40 mg, and a highly significant correlation was found between the logarithm of the creatinine clearance and the duration of daily furosemide ingestion. Cessation of furosemide and institution of a sodium-restricted diet was followed by improvement in the creatinine clearance. Three patients had acute renal failure with myoglobinuria. All patients examined showed tubular and/or interstitial changes. This study shows that in idiopathic edema, long-term furosemide treatment gradually impairs renal function, with reversal to a considerable degree after cessation of the drug, and that it causes organic changes in the kidney.

Adolescent↗
PubMed1983

Clinical pharmacokinetics of furosemide in children with nephrotic syndrome.

The pharmacokinetic disposition of furosemide has been investigated in seven children with nephrotic syndrome and in eight control children. Furosemide in plasma was analyzed by spectrofluorometry. After a single intravenous dose of furosemide (1 mg/kg body wt.) the nephrotic children showed lower initial plasma concentrations because of the larger volume of distribution. The mean half-life of furosemide in nephrotic children (38.5 +/- 7.8 min) was significantly longer than in the control group (28.0 +/- 7.7 min). The two groups did not differ in the body clearance of total furosemide. The average serum clearance was 4.95 +/- 1.7 ml/min/kg body wt. in the control group and 5.10 +/- 1.4 ml/min/kg body wt. in the nephrotic children. There was a significant reduction in urine sodium and distribution volume, whereas potassium excretion remained unchanged.

Child, Preschool↗
PubMedDate not supplied

High-dose cisplatin therapy using mannitol versus furosemide diuresis: comparative pharmacokinetics and toxicity.

The dose-limiting toxic effect of high-dose (100 mg/m2) cisplatin is renal insufficiency. Hydration with furosemide- or mannitol-induced diuresis has been reported to ameliorate this toxicity. Animal studies suggest that mannitol may be superior to furosemide in this regard. Twenty-two patients with advanced neoplasms refractory to conventional therapy were treated with cisplatin at a dose of 100 mg/m2 every 21--28 days. Patients were randomized to receive 37.5 g of mannitol by 6-hour infusion with cisplatin or 40 mg of furosemide prior to cisplatin therapy. Hydration with at least 1 liter of normal saline was given prior to cisplatin. Nephrotoxicity (creatinine greater than 2 mg/100 ml, creatinine clearance greater than 50 ml/minute) occurred in 19% of courses in the furosemide-treated group and in 28% of courses in the mannitol-treated group. Peak plasma platinum concentration, terminal half-life, urinary excretion, and percent protein-bound plasma platinum were similar in both groups. The use of cisplatin at this dose schedule resulted in similar toxicity and pharmacokinetics when using hydration with either furosemide or mannitol.

Adolescent↗
PubMed1982

Calcium-dependent stimulation of renal medullary prostaglandin synthesis by furosemide.

The present study examined the actions of furosemide and other "loop" diuretics on immunoreactive prostaglandin E (iPGE) and [14C]arachidonate (AA) release in vitro in incubates of slices from rat and dog outer or inner medulla. The loop diuretics furosemide, ethacrynic acid, bumetanide and 3-benzylamino-4-phenylthio-5-sulfamoylbenzoic acid all significantly increased [14C]AA and iPGE release (1.5- to 4-fold) into the media of rat outer and inner medulla and dog outer medullary slice incubates. By contrast, equimolar concentrations of chlorothiazide and hydrochlorothiazide were without effects on these parameters. Stimulation of [14C]AA or iPGE by furosemide was abolished by exclusion of Ca++ from the incubation media or by addition of verapamil to complete media, but was not altered by exclusion of Na+. Ca++-free media or verapamil also abolished the increases in [14C]AA and iPGE induced by ionophore A23187. By contrast, these incubation conditions did not influence the iPGE responses to hypertonic mannitol or exogenous AA. The presence of Ca++-responsive acyl hydrolase activity was demonstrated in the microsomal fraction from rat outer medulla. However, this activity was not altered by addition of furosemide to the subcellular fraction in the presence or absence of Ca++. Thus, furosemide and other loop diuretics stimulate renal medullary iPGE synthesis in vitro, and may do so through Ca++-mediated or dependent enhancement of the release of AA.

Amidohydrolases↗
PubMed1980

Furosemide intravenous infusion in normal man: electrolytic, metabolic and hormonal effects. Lack of changes in basal insulin and glucagon plasma levels.

Eight overnight fasted healthy young volunteers received an intravenous infusion of 0.5 mg furosemide per kg body weight administered in 60 min. This period was preceded and followed by two control periods of one hour each during which physiological saline (o.154 mol/l) was administered at a rate of 1 ml/min. Furosemide markedly increased the diuresis and natriuresis which reached 1260 +/- 198 ml and 138.4 +/- 20.9 mmol per hour respectively. This was associated with a significant three fold increase in urinary total catecholamines excretion. Blood glucose, plasma free fatty acids, insulin and glucagon concentrations did not exhibit any significant change during and after furosemide infusion, compared to pre-infusion values. These results demonstrate that, in normal man, doses of furosemide capable of exerting plasma concentrations. It is concluded that the stimulation of insulin and glucagon secretion observed in vitro with high furosemide concentrations (5 mmol/l) are not observed under usual therapeutic conditions.

Adult↗
PubMed1981

Penbutolol and furosemide in a fixed-dose combination-bio-equivalence of two formulations.

Twelve healthy male volunteers participated in an open cross-over study designed to test whether two fixed-dose combination formulations of penbutolol (40 mg) and furosemide (20 mg), an ordinary and a film-coated tablet, are bio-equivalent. Penbutolol capsules (40 mg) and 20 mg furosemide tablets (Lasix; Hoechst) served as reference formulations. The maximum concentration of furosemide was significantly depressed in the case of fixed-dose combinations, reflecting a possible pharmacokinetic interaction between penbutolol and furosemide. However, the area under the concentration versus time curve for furosemide and its cumulative urinary excretion and diuretic effect were not influenced by penbutolol. On the basis of plasma concentration versus time data and urinary parameters, the two fixed-dose formulations are bio-equivalent.

Adult↗