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PubMedDate not supplied

Comparative study of inhaled amiloride and inhaled furosemide in exercise-induced asthma.

BACKGROUND: Certain diuretics such as furosemide, when inhaled, have been found to be useful in preventing Exercise-Induced Asthma (EIA). STUDY OBJECTIVE: To assess the possible preventive effect of inhaled amiloride in EIA. DESIGN: A double blind, randomized, cross-over study comparing the effect of inhaled amiloride, inhaled furosemide and placebo in EIA. PATIENTS: Sixteen asthmatic patients (8 males and 8 females) with an average age of 21 years (range 9-31) who presented a FEV1 decrease of over 15% in a previous free-running exercise test. INTERVENTIONS: Solutions were inhaled with a Hudson nebulizer connected to an oxygen source in different days before exercise testing. A Vitalograph Compact (Ohmeda, England) spirometer was used and FEV1 was obtained at baseline, three minutes after solution inhalation, immediately after exercise and then every 5 min. until 20 minutes post-exercise. The changes in FEV1 percentages (FEV1%) and the mean FEV1 decreases expressed as percentages for each solution were compared. RESULTS: Inhaled furosemide diminished the fall in the FEV1 at every time after exercise. The maximum decrease in mean FEV1 was at 5 minutes post-exercise and was 11 +/- 7% with furosemide, 24 +/- 14% (p < 0.01) with amiloride and 19 +/- 12% (p < 0.05) with placebo. Amiloride administration resulted in a slight but significative increase in the FEV1 fall (p < 0.01 when compared with placebo). CONCLUSIONS: Amiloride is not useful to protect EIA whereas Furosemide does it. These differences results may be related to the differents mechanisms of action of the two diuretics.

Administration, Inhalation↗
PubMed1997

Dose-dependent cardiovascular, renal, and endocrine effects of furosemide in conscious lambs.

In recent experiments in conscious lambs, we showed that in addition to its well-known natriuretic and diuretic effects, i.v. injection of 2 mg/kg of furosemide resulted in a sustained increase in heart rate and an age-dependent increase in plasma renin activity. To determine whether these responses were dose dependent, we measured various parameters of cardiovascular, renal, and endocrine function in six chronically instrumented lambs. Three of seven doses of furosemide were tested at 48-h intervals; the range of doses was 0 to 7.5 mg/kg. A dose-dependent transient pressor response occurred within 20 min of furosemide administration; the duration of this response increased with increasing doses. Heart rate increased 40 min after doses of furosemide > or = 0.25 mg/kg; this response was not dose dependent. Renin increased following all doses; the peak and the duration of the renin response were dose dependent. These data provide new information on the dose-dependent cardiovascular, renal, and endocrine responses to furosemide in conscious newborn lambs.

Aldosterone↗
PubMed1997

Antiallergic potential of furosemide.

Recent reports have indicated the effectiveness of furosemide in inhibiting responses to inhaled allergen and in treating allergic conjunctivitis. In the present study furosemide was tested for its antiallergic potential using compound 48/80 induced paw edema and in vitro mast cell degranulation. Furosemide was found to significantly inhibit compound 48/80 paw edema and compound 48/80 induced histamine release. Furosemide was also found to inhibit histamine release during passive peritoneal anaphylaxis in rats. The results suggest that furosemide may be inhibiting the release of mediators of anaphylaxis from the mast cells.

Animals↗
PubMed1976

The effect of furosemide on potassium balance in open heart surgery.

Potassium balance was investigated in forty-five patients who underwent open-heart surgery. The patients were divided into a short-perfusion group (SPG, 24 patients) with a perfusion time shorter than 60 minutes and a long-perfusion group (LPG, 24 patients) with a perfusion time longer than 60 minutes. Nine patients in the SPG and 13 in the LPG received furosemide prophylactically prior to the perfusion. The furosemide dose was 20-60 mg. During the perfusion andpostoperatively all patients were given furosemide when necessary, i.e. when the urine output declined below 0.5 ml/kg/h. In both the short- and the long-perfusion groups potassium balance was negative on the day of operation and the following day. On the day of operation the patients in the SPG with furosemide prophylaxis had a negative potassium balance of 116 mmol and without prophylaxis of 33 mmol. The corresponding values in the LPG were 35 and 31 mmol. On the first postoperative day the values were 33 mmol and 50 mmol in the SPG and 29 mmol and 36 mmol in the LPG, respectively. The serum potassium level declined slightly in all the groups; the greatest decline was recorded for the SPG patients with prophylactic furosemide administration.

Adult↗
PubMed1976

Drug interactions in the horse: effect of furosemide on plasma and urinary levels of phenylbutazone.

Horses pretreated with 6.6 mg/kg of phenylbutazone were injected with 1 mg/kg of furosemide intravenously. Furosemide had no clinically significant effect on either plasma levels or plasma half-life of phenylbutazone. Furosemide reduced urinary levels of phenylbutazone 18-fold to concentrations which may result in inconsistent drug detection in routine screening tests. The results show that it is not possible to monitor compliance with phenylbutazone medication rules by means of urinalysis alone if the use of furosemide is permitted. Furosemide treatment, however, does not interfere with monitoring by plasma level determinations.

Animals↗
PubMedDate not supplied

Usefulness of inhaled furosemide in a bronchial asthma attack.

Furosemide administered through repeated dose inhalation has antiinflammatory effects on the airways. We carried out a study to measure the adjuvant effect of this drug with salbutamol inhalation in asthmatic patients presenting an acute or chronic asthma attack. We studied 50 patients, 25 of whom were given salbutamol (0.5%-1 cc) every 12 h and placebo every 12 h. All patients underwent spirometry on the first day and at the end of the treatment (5 days). Peak flow was recorded twice a day as well as daily diuresis and body weight. Peak flow in the morning increased 13.8 l/min in the group given salbutamol and placebo; in group given furosemide, the increase was 2.2 l/min, with statistically significant differences. Peak flow in the evening showed no sizeable differences. The same was true with spirometric variables (FVC, FEV1 and FEF 25-75), which improved greatly in both groups, but without a considerable difference. Diuresis increased in the group given furosemide (510.80 ml; in the group given placebo the increase was 310.20) without a significant difference. Analysis of body weight showed that in the group given furosemide average weight decreased from 140.4 to 138.5 lbs (52.4 to 51.7 kg); in the group given placebo, it increased from 130.3 to 132.6 lbs (48.6 to 49.5 kg). Statistical analysis was significant. We concluded that administering furosemide by inhalation for 5 days as adjuvant treatment to salbutamol in patients presenting with acute or chronic asthma attack is not superior to treatment using salbutamol and placebo.

Acute Disease↗
PubMed1996

Effects of Various Modalities of Oral Furosemide Administration in Mild or Severe Congestive Heart Failure.

BACKGROUND: This study evaluated the optimal formulation (tablet vs solution) and frequency (once vs twice daily) of maintenance oral furosemide in compensated congestive heart failure (CHF). METHODS AND RESULTS: Eighteen patients with mild (group 1) and 18 with severe (group 2) CHF were studied. On 2 consecutive days each patient's individual fixed oral furosemide daily dosage was administered in tablet or solution in a crossover design. In an additional study, 14 patients with severe CHF received the daily dosage in tablet or solution form in two divided doses. Pharmacokinetic data were obtained in six randomly allocated patients of each group, during the once daily administration periods of either formulation. Twenty-four-hour urinary sodium and 12-hour volume were significantly greater in group 1 following furosemide solution versus tablets. In group 2, all parameters were comparable in response to single identical doses in tablets or solution, as well as to once versus twice daily administration of either formulation. These results coincided with a higher C(max) and a shorter t(max) following solution. CONCLUSIONS: A once-daily oral furosemide solution is more effective than the same dosage in tablet form in patients with mild, but not those with severe, CHF. In patients with severe CHF, the natriuretic and diuretic effects are similar whether oral furosemide in tablet or solution is administered in a once or twice daily schedule.

Journal Article↗
PubMed1995

Furosemide Distinguishes Central and Peripheral Tinnitus.

The response of patients with tinnitus to the suppressive effects of IV furosemide is about 50%. Since furosemide is a drug without known effects on the central nervous system but with well documented effects in the auditory periphery, we hypothesized that it suppressed tinnitus of peripheral origin and that the response rate was due to that selectivity. To test this hypothesis we recruited 14 patients with unilateral tinnitus who had previously undergone either a labyrinthectomy or acoustic neuroma removal in the complaint ear. Tinnitus in these patients would most likely be of central origin. The first 12 patients tested were negative in response to IV furosemide as compared to the 50% response rate already documented. The last two patients had acoustic neuromas removed and were positive to IV furosemide. meaning that their tinnitus was suppressed. Examination of the case records of these latter two patients revealed that their cochlear portion of the VIIIn had been spared during surgery. We therefore suggest that IV furosemide selectively suppresses tinnitus of peripheral etiology.

Journal Article↗
PubMed2000

Inhaled furosemide in the treatment of acute exacerbations of asthma

Inhalation of the loop diuretic furosemide has been found to protect against challenges with bronchoconstrictive agents. OBJECTIVE: To determine if furosemide has any objective and/or subjective therapeutic effect on adult patients with acute exacerbations of asthma, above and beyond the effects of B2 agonists and oral glucocorticoids. METHODS: 35 adult patients with acute exacerbations of asthma were randomized and recruited into the study if they had a prior history of asthma, and <10 pack-year smoking history, had not received pre-hospital B2 agonists, were not pregnant, and had no sulfonamide allergy. A double blind study design was employed. One group received albuterol 5 mg with placebo and one group received albuterol 5 mg with furosemide 40 mg in their nebulizer. Both groups received prednisone 80 mg po. PEFRs were obtained before initiation of treatment and 30 and 60 minutes thereafter. A 10 point dyspnea scale was also employed at initiation of treatment and 30 and 60 minutes thereafter. Physicians were permitted to give rescue albuterol treatments as deemed necessary. RESULTS: There was no difference in the treatment arms with respect to PEFR, dyspnea score, or number of rescue albuterol treatments at 30 and 60 minutes. CONCLUSIONS: We found no statistical benefit to adding furosemide to a regimen consisting of prednisone and optimal doses of B2 agonist. We conclude that there is not a current role for furosemide in acute exacerbations of asthma.

Journal Article↗
PubMed1998

Fluctuations in blood lipid levels during furosemide therapy: a randomized, double-blind, placebo-controlled crossover study.

BACKGROUND: Acute decreases in intravascular volume are associated with increases in lipid levels. Furosemide causes acute changes in intravascular volume during prolonged therapy but is thought to have little effect on lipid levels. METHODS: To determine if there are daily acute rises in lipid and lipoprotein levels associated with changes in intravascular volume during long-term furosemide ingestion therapy, we performed a randomized, double-blind, placebo-controlled crossover study in 10 patients. RESULTS: In the 8 hours after furosemide ingestion there were increases in levels of plasma cholesterol (10.1%; P = .001), high-density lipoprotein cholesterol (9.0%; P = .006), and apolipoprotein B (9.8%; P = .003). The increases in levels of triglycerides (11.5%; P = .17) and apolipoprotein A-1 (13.3%; P = .051) were of similar magnitude but more variable and did not achieve statistical significance. There was no substantial change in the total cholesterol-high-density lipoprotein cholesterol ratio (0.6%; 95% CI,-0.74% to 8.6%; P =.88). CONCLUSION: This study indicates that there are acute increases in lipid levels after furosemide ingestion during prolonged therapy, which could affect the interpretation of lipid levels and cardiovascular risk in patients.

Aged↗
PubMed1999

Furosemide withdrawal improves postprandial hypotension in elderly patients with heart failure and preserved left ventricular systolic function.

OBJECTIVE: To assess the effects of furosemide withdrawal on postprandial blood pressure (BP) in elderly patients with heart failure and preserved left ventricular systolic function. METHODS: Noninvasive measurement of blood pressure (BP) and heart rate, computation of stroke volume and cardiac output (after a 1247-kJ (297-kcal) meal, and Doppler echocardiography before and 3 months after placebo-controlled withdrawal of furosemide therapy. RESULTS: Of 20 patients with heart failure (mean+/-SEM age, 75+/-1 years; left ventricular ejection fraction, 61%+/-3%), 13 were successfully able to discontinue furosemide therapy. At baseline, 11 (55%) of the 20 patients (had maximum postprandial systolic BP declines of 20 mm Hg or more. In the withdrawal group, the maximum systolic BP decline lessened from -25+/-4 to -11+/-2 mm Hg (P<.001) and the maximum diastolic BP from -18+/-3 to -9+/-1 mm Hg (P= .01), compared with no changes in the continuation group. In the withdrawal group, maximum postprandial declines in stroke volume and cardiac output decreased from -9+/-1 to -4+/-2 mL (P =.01) and from -0.6+/-0.2 to -0.2+/-0.1 L/min) (P = .04), respectively. The baseline maximum postprandial systolic BP decrease was correlated with the ratio of early to late flow (n = 20; Spearman rank correlation coefficient, 0.58; P = .007). For patients in the withdrawal group, the changes in postprandial systolic BP response were independently related to changes in peak velocity of early flow (n = 13; r2= 0.61; P = .003). CONCLUSIONS: Postprandial hypotension is common in elderly patients with heart failure and preserved left ventricular systolic function. The withdrawal of furosemide therapy ameliorates postprandial BP homeostasis in these patients, possibly by improving left ventricular diastolic filling.

Aged↗
PubMed1980

Indomethacin blocks acute audiologic effects of furosemide in Meniere's disease.

The acute audiologic effects of glycerin and furosemide were measured with and without indomethacin pretreatment in two patients. The positive effects of glycerin were not blocked by indomethacin. The positive effect of furosemide on discrimination score was blocked by indomethacin. The concomitant rise in plasma renin level after furosemide was also blocked by indomethacin. A role for prostaglandins in inner ear fluid dynamics is suggested by this study. It appears that glycerin and furosemide affect inner ear fluid dynamics by different mechanisms.

Aged↗
PubMed1985

Pulmonary and renal responses to furosemide in infants with stage III-IV bronchopulmonary dysplasia.

Pulmonary and renal responses to furosemide were evaluated in ten infants with stage III-IV bronchopulmonary dysplasia. Furosemide was given intravenously for two doses, 1 and 2 mg/kg, at approximately 24-hour intervals. The following indices were evaluated in series before and after entry into study: clinical respiratory distress syndrome score; blood pH; partial pressure of arterial carbon dioxide; alveolar-arterial oxygen gradient; urine output; glomerular filtration rate; fractional excretion of filtered sodium, chloride, potassium, and calcium; osmolar clearance; water clearance; and concentrations of serum electrolytes and calcium. A significant decrease in the respiratory distress syndrome score and in the partial pressure of arterial carbon dioxide was seen only transiently at two hours following each dose. There was no significant improvement in the alveolar-arterial oxygen gradient during the study. Furosemide induced diuresis and urinary excretion of sodium, chloride, potassium, and calcium. A significant decrease in serum chloride and potassium concentrations was seen at 48 hours after entry into study; serum sodium and calcium concentrations remained unchanged. This study has demonstrated that furosemide administration has only a short-term effect in the lung but has a potential for long-term complication on electrolytes and calcium balance in infants with well-established stage III-IV bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗
PubMed1998

Pharmacokinetic and pharmacodynamic changes of furosemide after intravenous and oral administration to rats with alloxan-induced diabetes mellitus.

Because some physiological changes occurring in diabetes mellitus patients could alter the pharmacokinetics and pharmacodynamics of the drugs to treat the disease, the pharmacokinetics and pharmacodynamics of furosemide were investigated after intravenous (i.v.) and oral administration of the drug (6 mg per whole body weight) to control rats and alloxan-induced diabetes mellitus rats (AIDRs). After i.v. administration, the total body clearance (5.47 versus 7.05 mL min(-1) kg(-1)) was significantly slower in AIDRs and this was due to significantly slower renal clearance (2.35 versus 4.33 mL min(-1) kg(-1)) because the nonrenal clearance was comparable between two groups of rats. The 8 h urinary excretion of furosemide after i.v. administration decreased significantly (2280 versus 3760 microg) in AIDRs due to impaired kidney function; the glomerular filtration rate measured by creatinine clearance was significantly slower (2.86 versus 4.33 mL min(-1) kg(-1)) and both the plasma urea nitrogen (43.5 versus 17.3 mg dL(-1)) and kidney weight (0.953 versus 0.749% of body weight) increased significantly in AIDRs. This resulted in a significant decrease in the 8 h urine output per g kidney (17.8 versus 43.6 mL) in AIDRs. However, the 8 h diuretic efficiency was not significantly different between two groups of rats. After oral administration, the area under the plasma concentration-time curve from time 0 to 8 h decreased significantly in AIDRs (1200 versus 1910 microg x min mL(-1)) due to considerably decreased absorption of furosemide from gastrointestinal tract of AIDRs. After oral administration, the 8 h urine output per g kidney (18.6 versus 36.4 mL) also decreased significantly in the AIDRs due to significantly decreased 8 h urinary excretion of furosemide (405 versus 2210 microg), however, the 8 h diuretic efficiency increased significantly (127 versus 35.2 mL mg(-1)) in AIDRs.

Administration, Oral↗
PubMedDate not supplied

Bioavailability of seven furosemide tablets in man.

A seven-way crossover study was conducted in 14 healthy male volunteers to evaluate the relative bioavailability of seven different marketed 40 mg furosemide tablets. Each dose was administered as a single tablet after an overnight fast, and blood samples were obtained for 16 hours. Plasma was assayed by HPLC. There were no statistically significant differences among the seven products for the mean peak concentration (1.01-1.29 micrograms/ml), mean time of peak (1.2-2.1 h) or mean area under the plasma concentration-time curves, which differed by less than 14 per cent. However, one product exhibited greater intersubject variability, and on this basis was considered inequivalent to the other six products. Furosemide is a potent and widely used diuretic. Currently the United States Food and Drug Administration (USFDA) has granted approval to at least twelve manufacturers of 40 mg furosemide tablets, based in part on bioavailability data obtained in human subjects. In addition, the USFDA has granted an 'AB' therapeutic equivalence evaluation to each of these products, which is understood by many to indicate the therapeutic equivalence and interchangeability of these products. The objective of the present investigation was to directly compare the bioavailability of seven 40 mg furosemide tablet products which had previously been approved by the Food and Drug Administration.

Adult↗
PubMedDate not supplied

Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide.

The pharmacokinetics and pharmacodynamics of furosemide were evaluated after intravenous administration of the same total dose of furosemide in different lengths of infusion time (10 s, 30 min, 2 h, and 8 h) to 6 dogs. The fluid loss in urine was immediately replaced volume for volume with intravenous infusion of Lactated Ringer's solution. The pharmacokinetic parameters such as per cent of the dose excreted in urine, total body and renal clearances, and terminal half-life were not significantly different with four different infusion times. The volume of distribution at steady state and mean residence time based on venous data, on the other hand, appeared to increase with increasing infusion time. The mean values for Vss were 0.334, 0.478, 0.499, and 0.708 1 kg-1 for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for MRT were 17.5, 22.2, 24.8, and 38.1 min. The diuretic effects (urine output and urinary excretion of sodium) were generally found to increase with increasing infusion times; the total mean 24 h urine outputs were 1102, 1464, 2190, and 3470 ml for 10 s, 30 min, 2 h, and 8 h of infusion, respectively, and the corresponding values for sodium excretion were 170, 175, 272, and 440 mmol. Furosemide plasma concentrations and hourly urinary excretion rates of furosemide, sodium, and potassium during the apparent steady state (between 2 and 8 h) in the 8 h infusion study were fairly constant.

Animals↗
PubMed1989

Simultaneous analysis of furosemide and bumetanide in horse plasma using high performance liquid chromatography.

A high performance liquid chromatographic method is described for the simultaneous determination of furosemide and bumetanide in horse plasma. The C8 (3 microns) reversed phase column (4.8 x 150 mm) provided clear separation of furosemide and bumetanide with other components present in the horse plasma. The detection limit for both the drugs was 10 ng/mL. Both drugs were stable in plasma (at natural or acidic pH) for up to 24 h. The method is sufficiently sensitive to detect furosemide levels in plasma obtained from horses receiving a therapeutic dose of furosemide.

Animals↗
PubMed2007

High-throughput liquid-chromatography method with fluorescence detection for reciprocal determination of furosemide or norfloxacin in human plasma.

A simple, high-throughput, highly selective and sensitive HPLC-FLD method for isolation and determination of furosemide and/or norfloxacin in human plasma samples following a simple organic solvent deproteinization step with acetonitrile as sample 'clean-up' procedure is reported. One of the two drug substances plays the internal standard role for the determination of the other. Separation of analyte and internal standard was achieved in less than 5.3 min (injection to injection) on a Chromolith Performance RP-18e column, using an aqueous component containing 0.015 mol/L sodium heptane-sulfonate and 0.2% triethylamine brought to pH = 2.5 with H(3)PO(4). The composition of the mobile phase was: acetonitrile-methanol-aqueous component = 70:15:15 (v/v/v) and the flow-rate was set up to 3 mL/min. The chromatographic method applied to the determination of furosemide relies on fluorescent detection parameters of 235 nm for the excitation wavelength, and 402 nm for the emission wavelength. In case of norfloxacin, the excitation wavelength is set up to 268 nm and the emission wavelength is set up to 445 nm. The overall method leads to quantitation limits of about 27 ng/mL for furosemide, and 19.5 ng/mL for norfloxacin, using an injection volume of 250 microL. The method was applied to the bioequivalence study of two furosemide-containing formulations.

Chromatography, High Pressure Liquid↗