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PubMedDate not supplied

A simple and rapid high-performance liquid chromatography method for determining furosemide, hydrochlorothiazide, and phenol red: applicability to intestinal permeability studies.

A simple reversed-phase high-performance liquid chromatography (HPLC) method with ultraviolet detection at 280 nm was developed for simultaneous quantitation of furosemide and hydrochlorothiazide along with phenol red as a nonabsorbable marker for in situ permeability studies in anaesthetized rats. A jejunal segment of approximately 10 cm was isolated and cannulated in both ends for inlet and outlet solution. The perfusate was collected every 10 min, and samples were analyzed using the developed method. The mobile phase was acetonitrile-water-triethylamine-glacial acetic acid (41.5 + 57.4 + 0.1 + 0.9, adjusted to pH 5.6) at a flow rate of 1 mL/min; the run time was 9 min. The calibration graphs were linear for all 3 compounds (r > 0.999) across the concentration range of 7.93-125 microg/mL for phenol red and 6.25-100 microg/mL for hydrochlorothiazide and furosemide. The limits of quantitation were 7.2, 8.9, and 6.8 microg/mL for furosemide, hydrochlorothiazide, and phenol red, respectively. The coefficients of variation for intraassay and interassay precision were less than or equal to 7.6%, and the accuracy was between 93.2-103.4%. Using the single pass intestinal perfusion technique and the suggested HPLC method for sample analysis, mean values of 0.25 x 10(-4) (+/-0.16) cm/s and 0.22 x 10(-4) (+/-0.13) cm/s were obtained for furosemide and hydrochlorothiazide, respectively.

Animals↗
PubMed1991

Biopharmaceutic evaluation of furosemide as a potential candidate for a modified release peroral dosage form.

An attempt was made to evaluate some of the criteria for developing a modified release peroral dosage form for furosemide which has a poor bioavailability when given in the conventional peroral dosage forms. The pathway of absorption for furosemide was studied ex vivo employing the Wilson-Wiseman test. Passive absorption was found to be the predominant mechanism of transport across the ileum of the guinea pig followed by active transport to the extent of about 17%. The in situ procedure to study the extent of absorption of furosemide from the various sites in the lumen of the gastrointestinal tract of the rat indicated the stomach to be the major site of absorption followed by the duodenum. It is hence postulated that due to the site-specificity and mechanism of absorption a peroral modified release dosage form having a longer gastric residence time could possibly increase the bioavailability of furosemide.

Administration, Oral↗
PubMed1991

Hepatic and renal metallothionein induction in the rat and mouse after treatment with furosemide.

Induction of hepatic and and renal metallothionein by furosemide was studied in the rat and mouse. Treatment of mice with 200 and 300 mg/kg furosemide elevated hepatic metallothionein by 117% and 366%, while renal metallothionein was induced by 29% and 380%, respectively. In the rat the drug was less potent i.e. liver metallothionein was increased by 167% and 217% following injection of 300 and 400 mg/kg furosemide, respectively, whereas kidney was not significantly changed by this treatment. The mouse hepatic and renal metallothionein was identified as zinc-containing thionein by Sephadex G-75 gel filtration (Ve/Vo = 2.0). In both species maximal induction was observed 24 hours post exposure. However, the mouse hepatic and renal metallothionein content declined after additional 24 hours whereas the rat metalloprotein was not reduced even after 72 hours of treatment. It is suggested that alterations in metal homeostasis may be responsible for hepatic and renal metallothionein induction caused by furosemide.

Animals↗
PubMed1991

Binding of furosemide to albumin isolated from human fetal and adult serum.

Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.

Adult↗
PubMed1990

Late effect of tobanum and tobanum + furosemide therapy on the glucose tolerance of patients and on the insulin response to oral glucose doses.

The authors examined the effect of beta-blocker monotherapy (Tobanum tab = 5 mg cloranololum hydrochloricum) and beta-blocker + diuretic (Tobanum + Furosemide) combination therapy on glucose tolerance and insulin secretion in response to oral glucose doses in hypertensive non-diabetic patients. Twenty-six patients were examined (13 men, 13 women). The patients were followed up for 28 weeks after a 2-week drug-free period. The hypotensive dose was adjusted individually within 4 weeks. Oral glucose tolerance test and immuno-reactive insulin determination were performed concurrently before starting hypotensive therapy and on weeks 6, 14, and 28 of therapy. The results of the examinations were evaluated separately in two patient groups. Fifteen patients were given daily 10-20 mg Tobanum (Group I) while 11 patients received daily 10-20 mg Tobanum + 40-80 mg Furosemide (Group II). The glucose area of patients on Tobanum monotherapy did not change, insulin secretion decreased gradually (from 804 to 495 pmol/l). The decrease was significant (p less than 0.05). The glucose area of Tobanum + Furosemide-treated patients increased from 13.2 +/- 3.2 mmol/l to 16.1 + 4.9, the insulin secretion decreased from 1039 + 339 to 706 + 411 pmol/l during therapy (p less than 0.02 and p less than 0.05, resp.). When evaluating the results the decrease of insulin secretion is attributed to Tobanum effect while the deterioration of glucose tolerance may be correlated to the action of Furosemide on extrapancreatic metabolism.

Adrenergic beta-Antagonists↗
PubMed1991

Comparison of the effects of torasemide and furosemide in nonazotemic cirrhotic patients with ascites: a randomized, double-blind study.

In a randomized double-blind trial we compared the effects of torasemide, a new loop diuretic, and furosemide in nonazotemic cirrhotic patients with ascites during a 3-day period in association with potassium canrenoate (200 mg/day) administration. Doses of loop diuretics administered in this trial (10 and 25 mg/day of torasemide and furosemide, respectively) had been shown to be equipotent in healthy subjects. Torasemide induced significantly greater natriuresis than furosemide (p less than 0.02), with a twofold greater percentage increase in basal values (day 1: 130% vs. 50%; day 2: 104% vs. 42%; and day 3: 65% vs. 26%, respectively). Body weight loss was significantly higher during torasemide (p less than 0.02) administration, and the overall decrease at the end of the treatment was twice as high for furosemide (2.5 +/- 0.6 kg vs. 1.3 +/- 0.4 kg, respectively). Diuresis was also higher during torasemide administration, but the difference was not significant (p = 0.08). The extent of kaliuresis observed during the two treatments was almost identical despite the striking differences in the natriuretic response. The effects of the two treatments on plasma electrolytes, creatinine clearance, blood urea nitrogen, mean arterial pressure, heart rate and plasma arginine vasopressin concentration were similar. Both drugs caused increases in plasma renin activity at the end of the treatment, whereas plasma aldosterone concentration slightly increased only after torasemide administration. Despite the presence of a trend toward a more pronounced effect on these parameters after torasemide administration, no significant difference between the two treatments was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascites↗
PubMed1990

[The effect of combined treatment in chronic congestive heart failure with digoxin, furosemide and pentoxifylline upon blood viscosity].

21 patients with symptoms of chronic congestive heart failure, NYHA classes II-IV, were treated with digoxin and furosemide for at least 14 days. In the next stage of the therapy they additionally received a 200 mg intravenous dosage of pentoxifylline and continued to take pentoxifylline orally for the period of at least 14 days. Before the therapy and after each of its stages echocardiography was performed, rheological and gasometric indices of the blood were determined and the level of physical efficiency was assayed in each patient according to NYHA classification. After the digoxin-furosemide treatment there was a significant increase in viscosity of the blood caused by its condensation. Simultaneously there could be observed a significant increase in physical efficiency in patients and also an improvement in some of indices of the left ventricular functions and in gasometric characteristics of the blood. Due to intravenous administration of pentoxifylline a decrease in blood viscosity occurred. The combined treatment with orally administered digoxin, furosemide and pentoxifylline caused a further decrease of blood viscosity, an improvement in some indices of left ventricular efficiency and gasometric characteristics of blood and also much better physical condition of the patients. The results of the present study show that in chronic congestive heart failure subjects a digoxin-furosemide treatment, besides undoubtedly advantageous haemodynamic effects, also leads to blood viscosity. The addition of pentoxifylline results the reduction of increased blood viscosity and in much better hemodynamic condition of the patients.

Adult↗
PubMed1988

[Furosemide-sensitive cation transport in frog skeletal muscle fibers].

Furosemide-inhibitable components in unidirectional cation fluxes have been identified in frog skeletal muscle. In sodium loaded muscles, placed in sodium-free rubidium lithium media, furosemide (1 mM) inhibits partially rubidium and lithium influxes as well as potassium and sodium outfluxes. The furosemide-inhibitable components were found to depend on the presence of ouabain. They were greatly diminished in sodium-free magnesium media and were present in chloride-free nitrate containing media. The dependence of furosemide-inhibitable sodium efflux on internal sodium content was also described.

Animals↗
PubMedDate not supplied

[Effects of furosemide on the excitability of the cerebral cortex].

The effect of furosemide on primary responses of the acoustic brain cortex of unrestrained cats was investigated. The responses were induced by electrical excitation of fibers of the thalamocortical radiation (TCR) and by sound excitation of various intensity and frequency. Furosemide at a dose of 18 mg/kg (intraperitoneally) did not modify primary responses to single stimulation of TCR fibers or their recovery. This diuretic produced an inhibitory effect on primary responses induced by sound excitation. Primary responses that developed in the acoustic cortex to sounds of a frequency of 10,000 Hz showed the highest sensitivity to furosemide. It was found that long-term (10 days) use of furosemide led to enhanced effects of the drug on primary responses to sound excitation.

Animals↗
PubMed1989

[Effects of hyperosmolarity and furosemide on resting membrane potentials and skeletal muscle fiber volume in rats].

The changes of the muscle fibres volume and resting membrane potential (RMP) were studied following treatment with hypertonic medium and furosemide. The volume changes in hypertonic medium began with cell shrinkage and later have been followed by the volume increase up to normal level during 30-40 minutes. At the same time the medium hypertonicity caused muscle fibres depolarisation. The hypertonic-induced decrease of the RMP was delayed in the furosemide-treated muscle. Besides, furosemide abolished the muscle fibres volume restorative properties in hypertonic medium. It is suggested that the membrane depolarisation and cell volume restoration in hypertonic medium are the resultant effects of intracellular chloride ions level elevation which, in turn, have been evoked by activation of furosemide-sensitive Cl(-)-influx system.

Animals↗
PubMed1989

The furosemide VOR test for Menière's disease. A preliminary report.

In order to easily detect endolymphatic hydrops and to avoid the side effects, we applied a furosemide VOR test in 24 patients with unilateral Meniere's disease, 6 patients with delayed endolymphatic hydrops, and 2 patients with labyrinthine syphilis. Immediately preceding an i.v. injection of 20 mg furosemide, and then 30, 60, 90 min after the administration, the VOR test was repeatedly performed. The slow-phase velocity in the VOR test was measured during harmonic sinusoidal rotation with eyes closed. Increased or decreased VOR-DP% beyond the normal range (10%) was referred to as positive. In 13 out of 24 cases (54%) with Menieres's disease, positive results were observed. Moreover, 4 out of 6 (67%) with delayed endolymphatic hydrops, one case out of 2 with labyrinthine syphilis were also positive in the furosemide VOR test. From these clinical investigations, we have concluded that the furosemide VOR test appeared to be another type of clinical test for the detection of vestibular endolymphatic hydrops.

Adult↗
PubMed1986

Effects of furosemide and indapamide upon pancreatic insulin and somatostatin secretion in vitro.

Antihypertensive treatment with furosemide and indapamide may eventually cause impairment of glucose metabolism. To study if this was due to a direct effect on the endocrine pancreas, we examined the effects of furosemide and indapamide on the release of insulin and somatostatin from the isolated perfused pancreas of normal dogs. Furosemide at concentrations ranging between 1-30 micrograms/ml inhibited insulin in a dose-dependent manner (2p less than 0.01) whereas the somatostatin secretion was left unchanged. Also the infusion of indapamide at doses ranging between 0.05-1 micrograms/ml subdued B-cell secretion at the two highest concentrations of 0.5 (by 15 +/- 2%, p less than 0.01) and 1 microgram/ml (by 22 +/- 5%, p less than 0.02) while pancreatic D-cell secretion did not alter. The results suggest, that furosemide and indapamide possess the ability to directly inhibit insulin secretion. Whether this effect is of clinical importance for the diminution in glucose tolerance observed during therapy remains, however, uncertain.

Animals↗
PubMed1988

Effects of ibopamine in combination with furosemide on renal function in patients with chronic congestive heart failure.

The effects of ibopamine and furosemide on renal function given alone and in combination at single doses were studied in 6 men and 6 women aged 45 to 73 years with chronic congestive heart failure of NYHA class II. After 3 days of dietary stabilization, the patients received either ibopamine 200 mg, furosemide 40 mg, or furosemide 40 mg plus ibopamine 200 mg with 2-day washout between treatments, according to a double-blind, balanced three-way crossover design using all possible treatment sequences. On each treatment day urine collections were performed at 2-hourly intervals from 2 h before to 6 h after dosing, and urine volume and Na+, K+, Cl-, and creatinine concentrations were measured for every period. The patients received a standardized breakfast 3 h before treatment and then were allowed 250 ml tap water to drink before starting each urine collection period. Venous blood samples were taken before breakfast and midway between each urine collection period for analysis of serum Na+, K+, Cl-, creatinine, and glucose. Heart rate, blood pressure, and physical signs were recorded 2, 1 h, immediately before, and then 0.5, 1, 2, 3, 4, 5, and 6 h after treatment. At the same times the patients were asked for any symptoms. The time course of the diuretic effect of furosemide 40 mg was consistent with the data reported by other authors.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Renal pharmacodynamic effects of torasemide and furosemide in normal man.

The effects of acute administration of torasemide (1-isopropyl-3-([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea), a new potent loop diuretic, were compared with those of furosemide in 8 healthy male volunteers (aged 22-35 years). The subjects were studied on two separate occasions, at 1-week intervals. After two baseline urine collections of 30 min, either torasemide (20 mg i.v.) or furosemide (40 mg i.v.) was given, followed by further timed urine collections after 15, 40 and 60 min. There were significant increases in urine flow, and in sodium, potassium, chloride and calcium excretion, which were maximal within 15 min after administration of both drugs. These effects were of similar magnitude except for the natriuretic and chloruretic actions which were more pronounced after furosemide than after torasemide (p less than 0.02). The drugs induced no significant changes in effective renal plasma flow or glomerular filtration rate, as measured from the clearances of constantly i.v. infused 123I-orthoiodohippuran and 51Cr-EDTA, respectively. Urinary dopamine, urinary prostaglandin E excretion and plasma renin activity were increased by both drugs. It is concluded that the acute effects of torasemide are comparable to those of furosemide.

Adult↗
PubMed1988

Comparative pharmacodynamics of torasemide and furosemide in patients with oedema.

The pharmacodynamics of torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea), a new potent loop diuretic, were compared to those of furosemide in a double-blind controlled study in 18 patients with oedema of various origin. Torasemide behaved like furosemide in exerting a potent diuretic effect which culminated during the first 4 h after its administration. Nevertheless, torasemide was about 8 times more potent, exerted a longer lasting diuretic effect and was more potassium sparing than furosemide. Torasemide did not accumulate during repeated administration (5 days). It was well tolerated and efficient in the treatment of oedema due to congestive heart failure and hepatic cirrhosis. The long duration of action and the potassium sparing effect of torasemide compared to furosemide are promising features of this new potent loop diuretic.

Aged↗
PubMed1988

High-dose furosemide in the treatment of refractory congestive heart failure.

Thirty-five patients with severe chronic congestive heart failure that was refractory to conventional therapy were given high dosages of furosemide (250 to 4000 mg/d) because of significantly reduced renal function (mean endogenous creatinine clearance, 0.53 mL/s/1.73 m2 [32 mL/min/1.73 m2]). Natriuresis, weight reduction (mean, 11 kg), and relief of symptoms were achieved in all patients. The mean survival after the start of the high-dose furosemide therapy was 11.3 months (range, 0.5 to 36 months) (n = 35). When this therapy eventually failed, long-term intermittent hemofiltration was performed in eight selected cases, further prolonging survival (mean, 3.0 months). High-dose furosemide therapy and hemofiltration improved the quality of life and prolonged survival. The use of diuretics in congestive heart failure should therefore include treatment with high-dose furosemide, which is effective and can be given over a long period without serious side effects.

Aged↗
PubMed1988

Lithium clearance as an indicator of proximal tubular sodium handling during furosemide diuresis.

To evaluate the use of the renal Li clearance as an indicator of proximal tubular Na handling during furosemide diuresis, clearance experiments were performed in conscious catheterized rats. Maximal depression of proximal Na reabsorption was induced by isotonic saline expansion (40 ml/hr) and under these conditions furosemide (7.5 mg/kg/hr) did not increase absolute or fractional clearance of Li. These results provide indirect evidence against the existence of a furosemide-sensitive Li reabsorption in the ascending limb of Henle. The increase of absolute and fractional Li clearance observed in nonexpanded animals given furosemide therefore most likely reflects inhibition of electrolyte reabsorption in the proximal tubules. Using Li clearance as a measure for Na output from the proximal tubules, the study provided information about the contribution of proximal and distal nephron segments to saline expansion natriuresis. The results indicate that the natriuresis is caused by enhanced delivery of Na from the proximal tubules, which is only partially compensated for by a load-dependent increase of absolute distal Na reabsorption, most likely occurring in the thick ascending limb of Henle.

Animals↗
PubMed1987

Study on the possible interaction between tenoxicam and furosemide.

A possible interaction between furosemide and the non-steroidal antiinflammatory drug (NSAID) tenoxicam was investigated in 12 patients (6 males, 6 females) with mild heart insufficiency and with a need for antiinflammatory treatment. The patients received once daily doses of 40 mg furosemide over 15 days. From day 6 onwards until day 13 tenoxicam was concurrently administered: 20 mg b.i.d. on days 6 and 7 and 20 mg once a day on days 8 through 13. On days 0 (pre-check), 1, 3, 5, 9, 12 and 15 vital parameters were measured and urine quantitatively collected to assess the elimination of a series of biochemical determinants. The urinary excretion profiles of furosemide and trough plasma levels of tenoxicam were measured on days 5, 9, 12 and 15. Vital parameters (blood pressure, heart rate, ECG and body weight) were not affected by tenoxicam. The urinary excretion of sodium and chloride tended to decrease during treatment with tenoxicam, but this effect was not significant. Tenoxicam caused a significant drop of prostaglandin E2 (PGE2) in 12-h urine of both gender: from 601 +/- 397 ng on day 5 to 264 +/- 117 ng on day 9 for men and from 128 +/- 78 ng on day 5 to 67 +/- 55 ng on day 9 for women. Creatinine clearance, beta 2-microglobulin clearance and urinary excretion of N-acetyl-glucosaminidase did not reveal evidence for acute renal impairment. The urinary excretion profile of furosemide was not significantly changed by concurrent dosing of tenoxicam. The drop in PGE2 excretion was likely a direct effect of tenoxicam on the synthesis of renal prostaglandins.

Acute Kidney Injury↗