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PubMed1979

Comparison of natriuretic and diuretic effects of single and divided doses of furosemide.

The natriuretic and diuretic effectiveness of once-daily and twice-daily furosemide administration schedules was compared in a two-way crossover study using six normal subjects. Urine was collected for 24hours before and after administration of the first dose of furosemide. Patients received one 40-mg dose or two 20-mg doses of the drug administered six hours apart. Sodium and potassium urine concentrations were measured through flame emission photometry using lithium as an internal standard. Chloride urine concentrations were determined using colorimetric measurement with mercuric thiocyanate. Results were statistically evaluated by a one-way analysis of variance. Results showed no statistically significant differences (p greater than 0.7) between the two regimens in the cumulative 24-hour excretion of sodium, potassium, chloride or water. The average 24-hour sodium excretion following a single 40-mg furosemide dose was 268.9 mEq, while that following administration of the two 20-mg doses was 294.2 mEq. Differences during various intervals within the 24-hour collection period were consistent with the relative sizes of doses administered. It would appear that single daily dose administration regimens would be a logical beginning for furosemide therapy, particularly when lower doses are being considered.

Adult↗
PubMed1995

Saturable first-pass kinetics, plasma protein binding, and the furosemide intricacies.

An equation for saturable nonlinear first-pass kinetics is presented to discuss some contra-intuitive findings encountered with furosemide bioavailability. The diverging effects on steady-state bioavailability (Fss) are simulated for changes in maximal metabolic capacity (Vm), volume of distribution (Vd), Michaelis constant (Km), steady-state plasma concentration (Css), repetitively administered drug dose (Dss), dosage interval (Tau), liver plasma flow (Ql), absorption rate constant (Ka), and free plasma fraction (fp), where (Cssf = fp Css = const.) and (Kmf = fp Km = const.). [Formula: see text] The present concept is in line with observations indicating that furosemide bioavailability decreases from 60 to 45% in nephrotic syndrome patients whose plasma protein binding is reduced and hepatic clearance increased. These observations and our equation-based simulations show that furosemide must have a first-pass effect. Hepatic extraction of furosemide is not facilitated by albumin, and saturable first-pass kinetics can not be used to explain an albumin paradox.

Animals↗
PubMedDate not supplied

Prevention of exercise-induced asthma in children using low doses of inhaled furosemide.

It has been demonstrated that inhaled furosemide inhibits indirect but not direct bronchoconstricting stimuli. The exercise test (ET; indirect) has been shown to be inhibited in adults. Our aim was to determine whether the ET was also inhibited in children by low doses of furosemide. We studied 10 asthmatic patients with a mean age of 11.1 years whose ET results were positive, and in whom the ET was repeated after inhaling 28 mg of furosemide. After 10 min, there were no significant signs of bronchodilatation. The percent decrease in mean FVC, FEV1, MF50 and peak flow (PF) was significantly lower with the premedication. The protection achieved was: FVC, 66.5%; FEV1, 51.4%; MF50, 30.3%; and PF, 63.9%. No clinical response was observed in 5 of 10 cases. It was concluded that 28 mg of inhaled furosemide inhibits the ET in asthmatic children.

Administration, Inhalation↗
PubMed1976

Natriuretic effect of furosemide after inhibition of prostaglandin synthetase.

The effects of furosemide on stimulation of renin secretion and urinary sodium excretion were studied in dogs pretreated with the prostaglandin synthetase inhibitors, indomethacin and meclofenamate. Pretreatment with these drugs failed to modify the natriuretic response to furosemide but completely blocked the rise in arterial plasma renin concentration produced by the diuretic. The organic acid probenecid did not affect either the natriuretic response or the increase in renin. In separate experiments, it was not possible to separate the effects of indomethacin on prostaglandin secretion, the renin-angiotensin system or renal hemodynamics. It is concluded that in the dog the natriuretic response to furosemide is not linked to the possible prostaglandin-induced increase in renal blood flow. Indomethacin apparently affects furosemide-induced renin secretion at both the vascular and macula densa sites. The data also suggest that the prostaglandins may be more important than the renin-angiotensin system in the modulation of intrarenal hemodynamics.

Animals↗
PubMed1977

Effect of furosemide on plasma fibrinolytic activity and urokinase excretion.

Plasma fibrinolytic activity, as measured by the fibrin-plate method, is enhanced after a single intravenous administration of 40 mg of furosemide. This effect becomes evident within 30 min and a peak response is attained 6 h after i.v. administration. On successive administration of furosemide, the fibrinolytic effect persists and the second peak becomes manifest again after 6 h. Following the parenteral administration of furosemide there is an initial decrease of urinary urokinase excretion which returns to a normal level after 3 to 6 h. Possible mechanisms which may explain the enhanced fibrinolytic activity after furosemide administration are discussed.

Endopeptidases↗
PubMed1994

[Effect of the administration of furosemide on the fluid filtration rate and in pulmonary artery pressure in isolated lungs of rabbits].

To study the possible effects of Furosemide at the lung level, two groups of isolated rabbit lung preparation were studied. An experimental group underwent a pulmonary hydrostatic oedema when the pressure of the left auricle (PAI) was increased from 0.45 +/- 0.74 t0 11.8 +/- 2.9 cm of H2O, with that increase in PAI we obtained an increase of 0.457 +/- 0.51 g/min in FFR (Fluid Filtration Rate), during this stable and sustained oedema, a 2 mg/Kg dosis of Furosemide was injected every 10 minutes and the possible changes in PAP, PAI, PVA, TFL, PaO2, PaCO2 and pH was observed, but no changes were observed in these parameters during the Furosemide infusion, and the same effect was observed in the control group were the preparations were maintained in basal conditions and without oedema. These results suggests that the Furosemide hat not a direct cardio-pulmonary effects, and the only possible effects could be by increasing diuresis at renal level.

Animals↗
PubMed1996

[Effect of furosemide on transperitoneal transport of guanidine derivatives: in vitro studies].

The transperitoneal transport dynamics (removal) of guanidinoacetic acid (GAA) and guanidinosuccinic acid (GSA) has been determined in vitro in the control conditions and after application of furosemide (10(-4) mmol/l) on the mesothelial side of the membrane. GAA peritoneal transfer values, as a rule, were higher than GSA and equaled at mean, in the control series of experiments 0.132 i 0.068 mg x 10(-4) x cm-2 x s-2, respectively. Furosemide decreased GSA passage in 30 min after it addition by about 30%, but GSA transfer diminished later, in 120 min., by about 37%. Therefore, mean GAA transport values before (30-90 min.) and after application of furosemide (120-210 min.) were not statistically significant differentiated, whereas GSA transport parameters were lowered by about 40%. Heterogeneity of the peritoneal GAA and GSA transport dynamics in the control series of the experiments, as well as in the series with furosemide, may be related to the physico-chemical differences (e.g. molecular mass) of the analysed derivates.

Animals↗
PubMed1998

Investigation on the bioequivalence of 2 oral preparations containing spironolactone and furosemide.

The bioequivalence of 2 formulations containing spironolactone and furosemide was determined. The test preparation was Spironolacton 50 plus Heumann tablets, a new generic spironolactone preparation, developed by Heumann Pharma GmbH, the reference preparation was Osyrol 50-Lasix capsules, Hoechst AG. The study was designed as a randomized 2-period, 2-sequence, crossover study. A daily dose of 50 mg spironolactone and 20 mg furosemide was administered over 5 days to 24 healthy volunteers in the fasting state. Plasma samples were assayed for spironolactone, its 2 active metabolites canrenone and 7alpha-thiomethylspirolactone, and furosemide by HPLC. Statistical analysis was performed by ANOVA and by nonparametric methods. Because spironolactone was rapidly eliminated from plasma, its pharmacokinetics could only be evaluated with regard to maximum plasma levels. This parameter did slightly miss the criteria for bioequivalence. For canrenone and 7alpha-thiomethylspirolactone bioequivalence was given. For furosemide the test formulation was found to be equivalent concerning the extent of bioavailability. Bioequivalence with regard to maximum concentrations could not be shown. However, from the point of view of pharmacodynamics, this finding may not necessarily be of clinical relevance.

Adult↗
PubMed1998

Comparative pharmacokinetics and pharmacodynamics of furosemide in Middle Eastern and in Asian subjects.

The pharmacokinetics and pharmacodynamics of a single oral dose of 40 mg furosemide has been compared in 11 healthy Middle Eastern Arabs with 12 Asian subjects under fasting conditions. There were no significant differences (p > 0.05) between the 2 ethnic groups in either the area under the plasma concentration time curve (AUC) or the time to maximal plasma concentration (tmax). The elimination half-life was significantly higher (p < 0.05) in Middle Eastern subjects (2.9+/-0.7 h) than in Asian subjects (2.2+/-0.6 h), while the maximal plasma concentration (Cmax) in Asian subjects (1,087+/-262 ng/ml) was significantly higher (p < 0.05) compared with Middle Eastern Arabs (776+/-163 ng/ml). The mean residence time (MRT) and the operative apparent volume of distribution (Vd/F) were significantly greater in Middle Eastern Arabs (4.5+/-0.9 h and 54.1+/-14.91) than in Asian subjects (3.6+/-0.8 h and 38.6+/-16.51). The difference between them in (Vd/F) abolished (p > 0.05) when corrected for body weight. The mean cumulative urinary excretion of furosemide in 8 h was 5.6 mg (range 1.6-15.2 mg) for Arabs and 6.1 mg (range 2.1-15.9 mg) for Asians. The relationships between furosemide-induced diuresis and furosemide, sodium, potassium, calcium, magnesium and chloride excretion rates appeared as a clockwise hysteresis loop indicating the development of tolerance during the course of drug action in both ethnic groups. No statistically significant differences (p > 0.05) were observed in the cumulative amounts excreted in urine of these electrolytes or their excretion rates between Arabs and Asians. The relationships between urinary excretion rates of sodium, potassium, calcium, magnesium, and chloride were linear with almost identical slopes for Arabs and Asians in each relationship.

Adult↗
PubMed1976

The effect of furosemide on renal blood flow and renal tissue oxygen tension in dogs.

The effect of furosemide (2 mg/kg i.v.) on blood flowin the renal artery and the tissue oxygen tension of the renal cortex and medulla was investigated in six dogs. The flow was measured with an electromagnetic flowmeter and the tissue oxygen tension with IBC tissue oxygen electrodes. The flow in the renal artery increased significantly (p less than 0.05) 5-15 minutes after furosemide administration. 40 minutes after the injection the flow had returned to its initial level. The tissue oxygen tension of both the cortex and the medulla showed significant elevation following furosemide administration. The maximum increase of tissue oxygen tension was recorded 10-20 minutes after the injection. The oxygen tension values exceeded the initial level by 22% in the cortex and by 48% (p less than 0.001) in the medulla. Simultaneously, with the changes in oxygen tension, urine output increase considerably and urine osmolality declined. Application of these renal effects of furosemide in clinical work, particularly in cardiopulmonary bypass surgery, is discussed.

Animals↗
PubMed1976

The effect of furosemide on the renal damage induced by toxic mushroom Cortinarius speciosissimus in the rat.

The effect of furosemide on the renal damage induced by the toxic mushroom Cortinarius speciosissimus was studied in female rats. Furosemide (50 mg/kg s.c.) was given 15 min before the mushroom administration (250 mg dried mushroom/kg body weight p.o.). It was observed that furosemide clearly increased the tubular damage induced by C. speciosissimus. In contrast, furosemide had no effect on the inflammation induced by this toxic mushroom.

Animals↗
PubMed1985

Comparison of extraction and precipitation methods for the HPLC determination of furosemide in plasma and urine.

Comparisons have been made between an ether extraction method and an acetonitrile precipitation method for the HPLC determination of furosemide (frusemide) in human plasma and urine. Recoveries of furosemide were 81-89% (ether extraction method for plasma), 73-103% (acetonitrile precipitation method for plasma) and 62-89% (ether extraction method for urine) for the concentration ranges studied. Values of correlation coefficients were 0.9998, 0.9991 and 0.9997 for standard curves for the three methods, respectively. Accuracy and precision (RSD) were: 92.4-114% +/- 3.57-20% for ether-extracted plasma; 98.1-103% +/- 3.47-19.9% for acetonitrile-precipitated plasma; and 103-107% +/- 4.03-13.2% for ether-extracted urine. Because of carryover of endogenous urine components, the acetonitrile-precipitation assay was unacceptable for urine. Furosemide was stable in frozen plasma for at least 113 days and in frozen urine for at least 204 days. No artifactual appearance of the hydrolysis product of furosemide, 4-chloro-5-sulfamoylanthranilic acid (CSA), was detected by the ether-extraction method under normal assay conditions.

Journal Article↗
PubMed2007

Desensitization therapy in a patient with furosemide allergy.

Allergy to furosemide is a rare phenomenon. Desensitization to this sulfa-containing drug has not been frequently performed. We describe a patient with severe congestive heart failure and type I allergy to furosemide. Because of the severity of her condition, we decided to use a rapid intravenous desensitization protocol. Following the desensitization, the patient was treated with intravenous and oral furosemide with a dramatic improvement in her clinical state. We suggest that rapid desensitization may be a safe and effective way of introducing furosemide to allergic patients for whom loop diuretics are urgently indicated.

Journal Article↗
PubMed1976

Unimpeded plasma renin increase after intravenous furosemide during saline replacement.

The effect on plasma renin activity of intravenous furosemide combined with saline replacement of the volume depletion was studied in twelve patients with insignificant heart disease. In ten of the patients the investigation was repeated without saline replacement. It was found that saline infusion, reducing or eliminating hemoconcentration, had no significant influence on the marked plasma renin increase. In eight of the patients the combined furosemide-saline study was performed during right-hear catheterization. Decrease in atrial pressures, known to occur within 15 min after furosemide intravenously, was virtually absent with the saline replacement. It is concluded that plasma volume reduction after intravenous furosemide is responsible for decreased filling pressures of the ventricles but not for plasma renin increase.

Adolescent↗
PubMed1997

Non-furosemide-related renal calcifications in premature infants with bronchopulmonary dysplasia.

Renal calcification is a known complication of long-term furosemide therapy in infants with bronchopulmonary dysplasia (BPD). In a prospective study the clinical course and long-term renal sequelae of renal calcifications of 19 consecutive premature neonates (birthweight < 1250 g) with bronchopulmonary dysplasia who did not receive furosemide were examined. Infants were divided into two different groups on the basis of ultrasound evidence of renal calcifications (RC group) or absence of renal calcifications (NRC group). Serial examinations, performed at the age of 1, 2, 3, 6, 9 and 12 months, showed that 12 infants at the mean age of 68.5 +/- 12.8 days of life had renal calcifications (63%), and 3 of them had nephrolithiasis; 8 had bilateral renal calcifications. Among the 9 survivors, 2 had chronic renal calcifications at the age of 9 months; however, all normalized at the age of 12 months. Twelve infants received hydrochlorothiazide and spironolactone (63%), 17 had prolonged courses of xanthines and dexamethasone (89.5%), while furosemide was not part of the routine pharmacological administration. Statistical analysis showed that birthweight, gestational age, Apgar score and length of parenteral nutrition were comparable in the RC and NRC group infants. Mean serum creatinine, creatinine clearance, fractional sodium excretion and urinary calcium excretion values during the 12-month study period were comparable in the RC and NRC groups. Mechanical ventilation and hospital stay length were instead associated with renal calcification occurrence. The strongest indicator of renal calcification risk for this high-risk population is the severity of the unresolved acute lung disease, where different facets of respiratory management, other than the addition of furosemide, represent sufficient stimuli and renal injury to potentiate stone formation.

Bronchopulmonary Dysplasia↗
PubMedDate not supplied

Acute tolerance development to the diuretic effect of furosemide in the rat.

Furosemide was given to rats as five different i.v. bolus doses (2.5-100 mg kg-1), or as an i.v. infusion to a steady-state concentration in plasma of 14 micrograms ml-1. The urinary furosemide excretion rate (delta Ae/delta t) and the diuretic effect (volume of urine) were measured. A parallel shift in the excretion-response curve was seen as a fivefold increase in (delta Ae/delta t)50 [delta Ae/delta t) at half-maximal effect) between the i.v. bolus doses from 2.5 to 40 mg kg-1. The slope factor did not change. During infusion, a decrease in efficiency to 20 per cent of the initial value was seen. These results are indicative of an acute tolerance development to the diuretic effect of furosemide. Some intrarenal feedback inhibition mechanism might be involved, as the extracellular fluid volume seems to be of great importance to the effect obtained. The resulting effect can be compared with the influence of a competitive antagonist.

Animals↗
PubMed1977

Effect of triamterene on potassium excretion in cirrhotic patients receiving furosemide.

In a three-way crossover study, 23 patients with hepatic cirrhosis, ascites, and dependent edema received 40 mg/day of furosemide alone and combined with triamterene 50 mg/day and triamterine 100 mg/day. Baseline potassium excretion did not increase when furosemide was given alone, but potassium excretion fell when 50 mg or 100 mg of triamterene was also given. Both doses of triamterene augmented the natriuretic effect of furosemide.

Chlorides↗
PubMed1977

Digoxin kinetics during furosemide administration.

The urinary excretion of a 0.75-mg oral dose of digoxin was assessed in 8 healthy men during a control 5-day period and then, after a washout period of at least 2 wk, during a 5-day period when the subjects also took oral furosemide, 40 mg daily. Analysis of the raw data by a paired Student's test and analysis of variance of log-transformed urinary digoxin excretion data revealed no significant difference attributable to the addition of furosemide (F = 1.16; df = 1,21). The treatment by day interaction showed the slopes to be consistent between the two treatments. It seems that in the presence of normal renal function there is no need to alter loading or maintenance doses of digoxin when furosemide is also given. Analysis of variance with log transformation of data is suggested as a practical approach to handling digoxin urinary excretion results when the transformation linearizes the data through examination by the method of orthogonal polynomials.

Adult↗