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PubMed1979

Effect of furosemide in canine low-pressure pulmonary edema.

We studied the effect of furosemide on pulmonary oxygen exchange, lung liquid, and central hemodynamics in dogs with pulmonary capillary leak induced by intravenous oleic acid (OA). 2 h after OA, triple indicator-dilution lung liquid volume and pulmonary shunt (Qs/Qt) doubled despite normal pulmonary capillary wedge pressure in 16 dogs compared with dogs not given OA in which no variable change during the same time. Six edematous dogs were then treated with furosemide (1 mg/kg), and 2 h later they showed significant reductions in Qs/Qt and lung liquid. In contrast, six other edematous dogs not given furosemide increased Qs/Qt and lung liquid during the same time. The changes in edema after furosemide could not be attributed to altered wedge or colloid osmotic pressures, and similar changes in Qs/Qt and lung liquid with furosemide were observed in four nephrectomized dogs. We conclude that pulmonary vasoactive effects of furosemide account for reduced shunt and edema in canine pulmonary capillary leak. These effects of furosemide differ from those in cardiogenic pulmonary edema, and suggest a different rationale for diuretic therapy in low-pressure pulmonary edema. Analysis of count rates from 51Cr-labeled erythrocytes and 125I-labeled albumin in lungs excised from 12 dogs indicated that the composition of excess lung liquid did not change with furosemide, and was 50% plasma, 25% blood, and 25% crystalloid.

Animals↗

PubMed1990

Effect of high-dose furosemide in refractory congestive heart failure.

High-dose firosemide is considered effective in primary renal sodium retention but is not generally recommended in congestive heart failure. In order to evaluate efficacy and safety of high-dose furosemide (greater than 500 mg/day), the authors studied 20 patients (pts) resistant to therapy (including furosemide less than 500 mg/day) selected from 161 pts admitted for chronic heart failure. All refractory pts (15 men and 5 women, mean age sixty +/- 12 years) were in NYHA class IV and showed hyponatremia (130 +/- 5 mEq/L) and impaired renal function (BUN 31 +/- 14 mg/dL, serum creatinine 1.3 +/- 0.3 mg/dL and BUN/creatinine ratio 23 +/- 7). In addition to digitalis, dopamine, angiotensin-converting enzyme inhibitors, or vasodilators, IV high-dose furosemide (775 +/- 419 mg/day, 500-2000) was given for ten +/- five days under daily clinical and laboratory monitoring. Three pts died of low-output syndrome while 16 pts were upgraded to NYHA class III and 1 pt to class II; a mean weight reduction of 7.3 +/- 2.9 kg in ten + five days (0.80 +/- 0.4 kg/day) and a mean diuresis increase of 88 +/- 57% occurred. The maximal dose of furosemide did not correlate with serum creatinine but did correlate with BUN/creatinine ratio (r = 0.78, p less than .001). Pts were discharged on with chronic heart failure, and 43% in the subgroup in NYHA class IV with hyponatremia. High dose furosemide was effective for rapid removal of excess water and salt in "furosemide-resistant" congestive heart failure. The relationship between renal impairment and maximal furosemide doses seems to confirm the role of renal pharmacokinetics in the appearance of furosemide resistance.

Administration, Oral↗

PubMed1985

The effects of piretanide on catecholamine metabolism, plasma renin activity and plasma aldosterone: a double-blind study versus furosemide in healthy volunteers.

In a double-blind, crossover study, 8 male volunteers (mean age: 25.9 years) received successively 6 different regimens of two diuretics, piretanide and furosemide, with a 1-week wash-out period between each drug regimen. Piretanide (6 mg) or furosemide (40 mg) were given either once daily at 08.00 hours or twice daily at 08.00 and 12.00 hours or at 08.00 and 20.00 hours. Each of these phases lasted for 1 week. Serial measurements were performed on plasma renin activity, plasma aldosterone, plasma adrenaline, plasma noradrenaline, plasma dopamine, cumulative urinary excretion of aldosterone, urine volume and urine osmolality. Plasma catecholamines showed no clinically relevant changes during all three regimens of piretanide or furosemide dosage. Piretanide and furosemide both induced a short-term increase in plasma renin activity with a maximum about 4 hours after dosing which returned to initial levels after approximately 12 hours regardless of whether a single or twice daily dose had been given. After 1 week of piretanide given once daily, lower plasma renin activity was found than after furosemide. Furosemide given once daily caused higher plasma aldosterone concentrations than did piretanide. The lowest plasma aldosterone concentrations were found during the twice-daily piretanide regimen at 08.00 and 20.00 hours. Aldosterone excretion in urine was also higher during furosemide than during piretanide administration. Piretanide given twice daily at both 08.00 and 12.00 hours or 08.00 and 20.00 hours caused the most insignificant changes in aldosterone excretion. It is suggested that piretanide, in comparison to furosemide, activates the counter-regulatory mechanisms, which may diminish the antihypertensive effect of the diuretic, to a much lesser extent.

Adult↗

PubMed2006

The changes in renal function after a single dose of intravenous furosemide in patients with compensated liver cirrhosis.

BACKGROUND: Patients with compensated Child-A cirrhosis have sub clinical hypovolemia and diuretic treatment could result in renal impairment. AIM: To evaluate the changes in renal functional mass as reflected by DMSA uptake after single injection of intravenous furosemide in patients with compensated liver cirrhosis. METHODS: Eighteen cirrhotic patients were divided in two groups; eight patients (group 1, age 56 +/- 9.6 yrs, Gender 5M/3F, 3 alcoholic and 5 non alcoholic) were given low intravenous 40 mg furosemide and ten other patients (group 2, age 54 +/- 9.9, Gender 6M/4F, 4 alcoholic and 6 non alcoholic) were given high 120 mg furosemide respectively. Renoscintigraphy with 100MBq Of Tc 99 DMSA was given intravenously before and 90 minutes after furosemide administration and SPECT imaging was determined 3 hours later. All patients were kept under low sodium diet (80mEq/d) and all diuretics were withdrawn for 3 days. 8-hours UNa exertion, Calculated and measured Creatinine clearance (CCT) were performed for all patients. RESULTS: Intravenous furosemide increased the mean renal DMSA uptake in 55% of patients with compensated cirrhosis and these changes persist up to three hours after injection. This increase was at the same extent in either low or high doses of furosemide. (From 12.8% +/- 3.8 to 15.2% +/- 2.2, p < 0.001 in Gr I as compared to 10.6% +/- 4.6 to 13.5% +/- 3.6 in Gr 2, p < 0.001). In 8 patients (45%, 3 pts from Gr 1 and 5 pts from Gr 2) DMSA uptake remain unchanged. The mean 8 hrs UNa excretion after intravenous furosemide was above 80 meq/l and was higher in Gr 2 as compared to Gr 1 respectively (136 +/- 37 meq/l) VS 100 +/- 36.6 meq/l, P = 0.05). Finally, basal global renal DMSA uptake was decreased in 80% of patients; 22.5 +/- 7.5% (NL > 40%), as compared to normal calculated creatinine clearance (CCT 101 +/- 26), and measured CCT of 87 +/- 30 cc/min (P < 0.001). CONCLUSION: A single furosemide injection increases renal functional mass as reflected by DMSA in 55% of patients with compensated cirrhosis and identify 45% of patients with reduced uptake and who could develop renal impairment under diuretics. Whether or not albumin infusion exerts beneficial effect in those patients with reduced DMSA uptake remains to be determined.

Aged↗

PubMed1995

Furosemide treatment, angiotensin II, and renal growth and development in the rat.

Diuretics are commonly used to treat a variety of conditions, including progressive nephropathies, cardiovascular, and pulmonary diseases. Such treatment stimulates the production of angiotensin II, an important mediator of renal growth which may accelerate progressive glomerulosclerosis. To further study the effects of diuretic treatment on normal renal growth and development, weanling male Munich-Wistar rats received no drug, enalapril, furosemide, or both drugs for 6 wk; morphometric studies were then performed using standard light and electron microscopic techniques. Plasma renin activity was elevated by furosemide treatment. Cortical tubular growth was stimulated in rats receiving furosemide or both drugs; enalapril did not affect cortical tubular growth when compared with untreated animals. Glomerular volume was increased in furosemide-treated animals, primarily due to an increase in the proportion of mesangial cells, whereas enalapril decreased glomerular volume. Furosemide also increased the filtration surface area per glomerulus whereas enalapril decreased it. Concurrent enalapril treatment blocked the furosemide-induced changes in filtration surface area as well as attenuating overall glomerular and mesangial growth. Glomerular changes correlated with plasma renin activity. Furosemide stimulated glomerular growth, especially of mesangial cells, probably via stimulation of AngII production. Given the relationship of mesangial cell growth and progressive renal disease, diuretic therapy could thus accelerate glomerulosclerosis. Cortical tubular growth also increased with furosemide; however, enalapril had no effect, so factors besides angiotensin II appeared to modulate tubulointerstitial growth in these animals.

Analysis of Variance↗

PubMed1988

Plasma renin and prorenin (inactive renin) in diabetes mellitus: effects of intravenous furosemide.

PRA, active renin, and prorenin were measured in 32 normotensive diabetic patients and 14 normal subjects of similar ages before and after iv injection of 40 mg furosemide. The majority of the diabetic patients had normal PRA and active renin levels before and after furosemide, but in 4 normal subjects and 5 diabetic patients PRA did not rise after furosemide treatment to at least 0.25 ng angiotensin I/(L.s) as previously found in 90% of normal subjects. Two thirds of the diabetic patients had higher plasma prorenin levels than the normal subjects. Four of the 5 diabetic patients whose PRA failed to rise to the usual level after furosemide treatment attained a plasma prorenin level higher than any normal subject, suggesting that furosemide stimulated synthesis and secretion of prorenin, but that conversion of prorenin to active renin was impaired. These 5 diabetic patients also had higher plasma creatinine and potassium levels as well as an increased frequency of albuminuria compared with the other diabetic patients. In contrast, the 4 normal subjects whose PRA failed to reach the usual level after furosemide treatment had low unresponsive prorenin levels, indicating that furosemide did not evoke the expected increase in prorenin or renin synthesis. We conclude that the inability of some diabetic patients to increase PRA after furosemide treatment is not dependent on failure of renin synthesis, but reflects an impairment of the normal processing of prorenin, leading to high levels of prorenin in plasma.

Adult↗

PubMed2001

Improvement in site-specific intestinal absorption of furosemide by Eudragit L100-55.

Furosemide (frusemide) is a weakly acidic diuretic drug. Its absorption is poor and variable, in part due to its restricted sites of absorption, mainly the stomach. The narrow absorption window of this drug can be explained by pH partition theory. The purpose of this study was to investigate the feasibility of widening the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract with officially used additives. Methacrylate copolymer (Eudragit L100-55), hydroxypropylmethylcellulose phthalate (HP-55) and hydroxypropylmethylcellulose acetate succinate (AS-MF) were selected as additives. The pH of suspensions of these additives was about 4, and the pH was adjusted to about 6-7 by the addition of NaOH. The Eudragit L100-55 suspension was found to be the most resistant to NaOH titration. When Eudragit L100-55 was used in an in-situ ileal loop experiment in rats, the pH of the intestinal contents was significantly reduced, from 7.9+/-0.1 to 5.7+/-0.1, and the plasma concentration of furosemide 15 min after administration was about 3 times higher than that in controls, 1.81+/- 0.42microg mL(-1) vs 0.63+/-0.08 microg mL(-1). However, the plasma concentration of [14C] mannitol was not changed by the co-administration of Eudragit L100-55. Furthermore, the AUC of furosemide was significantly increased by a factor of about 1.6 relative to that in controls by the co-administration of Eudragit L100-55, to 21.4+/-4.0 microg h mL(-1) from 13.3+/- 3.9 microg h mL(-1), and the gastrointestinal pH in the midgut and ileum was significantly reduced, with most of the furosemide remaining in these segments at 2 h following the oral administration of furosemide with Eudragit L100-55 to rats. These findings clearly demonstrate that the addition of Eudragit L100-55 can increase the absorption of furosemide in distal portions of the gastrointestinal tract. In conclusion, it is feasible to widen the absorption window of furosemide by controlling the pH in distal portions of the gastrointestinal tract by the co-administration of Eudragit L100-55.

Animals↗

PubMed1982

Renin response to furosemide differs with the routes of administration in health men.

Plasma renin activity (PRA) was serially determined 0, 15, 30, 60 and 120 min following administration of furosemide in a dose of 40 mg intravenously (i.v.) and 80 mg orally (p.o.) at a one week interval in 10 healthy men. Following i.v. furosemide administration, PRA increased rapidly and reached a plateau level of 6.1 +/- 1.0 ng/ml/h (222 +/- 44% of the control), at 15 min and remained at about the same level throughout the remaining period of the study. In contrast, PRA increased progressively to a maximum level of 5.5 +/- 0.7 ng/ml/h (285 +/- 53% of the control), 120 min after p.o. furosemide. In case of p.o. furosemide, the increase in PRA was dependent on the doses used per body weight, and was significantly correlated with the cumulative sodium excretion by itself, or the cumulative sodium excretion adjusted by either the leanness index or the body surface area. Such relationships were not apparent after i.v. furosemide. These findings suggest that the response of renin release to furosemide in healthy men differs with the routes of administration and renin release with p.o. furosemide may be largely due to a net sodium loss, while mechanism(s) other than sodium loss may be involved in the early hypersecretion of renin with i.v. administration of furosemide.

Administration, Oral↗

PubMed1992

Daily variation in the effects of furosemide in rats.

Daily variation in the effects of furosemide, a loop diuretic agent, was examined in Wistar rats maintained under conditions of light from 7 a.m. to 7 p.m. and dark from 7 p.m. to 7 a.m. Furosemide (30 mg/kg) was given orally at 12 p.m., 4 a.m., 8 a.m., 12 a.m., 4 p.m. or 8 p.m. Urine was collected for 8 hr after furosemide administration, and urinary excretions of sodium and furosemide were determined. There were significant daily variations in the urine volume and urinary excretions of sodium and furosemide with a peak at 8 a.m. and a trough at 12 p.m. Significant correlations were observed between the urinary amount of furosemide and its diuretic effects (urine volume and urinary sodium excretion). These results suggest that the diuretic effects of furosemide show daily variations which are, at least in part, caused by the daily variation in the urinary excretion of furosemide.

Animals↗

PubMed1993

Low-dose atrial natriuretic factor and furosemide in experimental acute congestive heart failure.

This study was designed to address three objectives in an experimental model of acute congestive heart failure (CHF) in the dog produced by rapid ventricular pacing. The first objective was to characterize cardiorenal and humoral responses before and during 2 h of acute CHF. The second objective was to determine the modulating action of iv furosemide upon these biologic responses to acute CHF, testing the hypothesis that furosemide-mediated natriuresis is associated with activation of the renin-angiotensin-aldosterone system (RAAS) compared with the control group. The third objective was to determine the modulating action of continuous low-dose atrial natriuretic factor (ANF) administration during acute CHF upon these biologic responses, testing the hypothesis that exogenous low-dose ANF would prevent activation of the RAAS and enhance the natriuretic action of furosemide. In the control group (Group 1; N = 6), plasma ANF increased after the onset of CHF; GFR and sodium excretion were maintained without activation of this RAAS despite arterial hypotension. In Group 2 (N = 6), furosemide in acute CHF increased sodium excretion but in association with a decrease in GFR and activation of the RAAS. Low-dose exogenous ANF and furosemide (Group 3; N = 6) in acute CHF were associated with a maintenance of GFR, no activation of the RAAS, and potentiation of furosemide-induced natriuresis. In summary, these studies demonstrate that furosemide potently increases sodium excretion in acute CHF, but with a decrease in GFR and activation of the RAAS. Low-dose ANF in acute CHF with furosemide maintains GFR, attenuates activation of the RAAS, and potentiates natriuresis.

Acute Disease↗

PubMed1996

Dopamine does not enhance furosemide-induced natriuresis in patients with congestive heart failure.

The objective of this study was to determine whether the addition of low-dose (renal-dose) dopamine to furosemide therapy enhances natriuresis in patients with compensated congestive heart failure, New York Heart Association Class II or III. We performed a randomized, controlled, open-label, crossover study wherein urinary sodium, creatinine, and furosemide excretion rates and GFR determined by inulin clearance rates were measured during each of three treatment interventions: furosemide infusion alone, dopamine infusion alone, and furosemide and dopamine infusions administered concurrently. Six of eight recruited subjects (4 male, 2 female) were able to complete the study. The baseline sodium excretion rate after equilibration on a metabolic diet was 6.7 +/- 0.7 mEq (mean +/- SE) over 3 h. Infusion of dopamine alone caused a slight nonsignificant increase in natriuresis to 36.7 +/- 8.5 mEq/3 h. Furosemide alone markedly increased sodium excretion to 276.6 +/- 47.2 mEq/3 h. No significant additional increment in natriuresis occurred when dopamine and furosemide were administered concurrently (253.8 +/- 73.6 mEq/3 h). Neither dopamine, furosemide, or their coadministration affected GFR. In conclusion, infusion of low-dose dopamine does not enhance furosemide-induced urinary sodium excretion rates in patients with compensated congestive heart failure, New York Heart Association Class II or III.

Aged↗

PubMed2002

Furosemide protective effect against airway obstruction.

Furosemide (frusemide) is mainly employed as a powerful diuretic that inhibits Na and K reabsorption in renal tubules. However other valuable pharmacological effects have been discovered that include a protective action from bronchospasm. The effects of furosemide on airways have been recognized to be more and more complex as far as an increasing amount of studies have been produced on this subject. The drug shows no acute bronchodilator effect, but prevents or attenuates bronchospasm caused by many factors, such as hyperpnea, drugs (metabisulphite, bradykinin, AMP), physical agents (hypo- and hypertonic aerosols), and allergen challenge in asthmatic patients. Furosemide is also active on upper airway mucosa, on which the drug decreases nasal resistance in patients affected by non-allergic rhinitis and exhibits a protective effect on nasal mucosa reactivity to the specific allergen in atopic subjects. The mechanism of action of furosemide on airways has not yet been fully cleared and interference with electrolyte epithelial transport, prostaglandins, inflammatory cell activity, vascular and neural regulation has been hypothesized. The interest for clinical application of inhaled furosemide has grown in last years. Some Authors have investigated whether the drug is effective in acute asthma attacks or not. Furosemide is one of the drugs currently used to prevent exercise-induced asthma. More recently, inhaled furosemide has been observed to decrease the sensation of experimentally-induced dyspnea. Apart from possible therapeutic application, studies about furosemide effects on respiratory mucosa can contribute to better understand the physiology of upper and lower airways.

Administration, Inhalation↗

PubMed1997

Effect of bolus injection versus continuous infusion of furosemide on diuresis and neurohormonal activation in patients with severe congestive heart failure.

Previous studies have demonstrated that continuous infusion of furosemide results in increased diuresis and natriuresis compared with bolus administration of the drug in patients with severe heart failure. We reasoned that continuous infusion of furosemide caused less activation of neurohumoral mechanisms, since other studies have shown that bolus administration of furosemide may activate this system. We therefore tested the hypothesis that continuous administration of furosemide would increase water and sodium excretion due to less activation of neurohormones. Eight patients with severe heart failure were studied during continuous infusion over 24 h and bolus injections of furosemide twice daily in a randomized cross-over study. Bolus administration of furosemide increased diuresis and natriuresis significantly in the first 4 h after administration compared with continuous administration, but this was later reversed, resulting in similar 24 h total output. The neurohormones measured at baseline were all markedly elevated. Neither regimens of furosemide caused any further significant changes in neurohumoral response except that pro-ANF decreased more during the first 8 h after bolus administration compared to continuous infusion. This study has demonstrated that bolus administration of furosemide in conventional doses is equally effective as continuous intravenous infusion in patients with severe heart failure. This may be due to maximal neurohormonal activation in severe heart failure (NYHA III-IV) which could not be further activated by bolus administration.

Atrial Natriuretic Factor↗

PubMed1998

Effect of inhaled furosemide in acute asthma.

We assessed the acute bronchodilator effect of nebulized furosemide when added to conventional therapy of acute emergency department (ED) asthma. Using a double-blind design, 42 patients with acute asthma were randomized to receive 2.5 mg nebulized salbutamol and either 40 mg of nebulized furosemide or saline solution. We recorded clinical variables (respiratory rate, heart rate, and pulsus paradoxus) and peak expiratory flow rates (PEFR) before and 15 and 30 min after therapy. We found no significant difference in PEFR between salbutamol/furosemide and salbutamol/saline-treated patients 15 and 30 min following inhalation. Other endpoints were equally unaffected. However, when we examined separately those patients whose exacerbations were of relative short duration (< 8 hr), PEFR improved significantly more in the furosemide-treated group. At 15 min, PEFR increased by 82 +/- 48% in the furosemide group compared to 35 +/- 40% in the control group (p = 0.03), an effect that was also evident at 30 min when PEFR had increased by 113 +/- 49% in the furosemide group versus 61 +/- 35% in the control group (p = 0.014). Respiratory rate, heart rate, and pulsus paradoxus improved with no differences between the groups. The beneficial effect of furosemide was not evident in patients who reported more prolonged duration (> 8 hr) of asthmatic symptoms. The response to furosemide appeared to be unrelated to concomitant ED therapy with corticosteroids, to baseline pulmonary function, or to patient demographic variables. We conclude that furosemide may offer additive bronchodilator benefits in acute naturally occurring asthma of relative short duration.

Adult↗

PubMed2005

Attenuation of the kaluretic properties of furosemide by triamterene (Dyrenium) in healthy volunteers.

OBJECTIVE: To examine if concomitant administration of furosemide, a loop diuretic, with the potassium- and magnesium-sparing diuretic triamterene would decrease loss of potassium and magnesium while improving diuresis. METHODS: In this open-label, three-way crossover study, healthy subjects were randomized to receive treatment with 40 mg furosemide, with 150 mg triamterene, or treatment with 40 mg furosemide and 150 mg triamterene. Urine samples were collected 24 hours before dosing and between 0 - 1, 1 - 2, 2 - 3, 3 - 4, 4 - 6, 6 - 8, 8 - 12, and 12 - 24 hours post-dosing. Sodium and potassium levels were measured by an ion-selective electrode method. Magnesium was measured colorimetrically using a xylidyl blue reaction. RESULTS: Co-administration of furosemide with triamterene resulted in enhanced diuresis, particularly in the first 0 - 12 hours post-dose, compared with either furosemide or triamterene alone. Compared to individual treatments, combination therapy significantly increased urinary sodium excretion (p = 0.0001) while significantly decreasing urinary potassium excretion (p = 0.0001); importantly, the magnesium-sparing characteristic of triamterene was retained with furosemide co-administration. CONCLUSION: Triamterene, when used in combination with the loop diuretic, furosemide, preserves intracellular potassium and magnesium while enhancing the natriuretic effect of furosemide.

Adolescent↗

PubMed1976

[Age dependent differences in the pharmacokinetics of furosemide in rats].

After i.p. administration of 0,60 mg/100 g of furosemide, adult rats excreted 50 to 70% of this diuretic drug unchanged and 10% as desfurylmethylfurosemide. The renal excretion of furosemide is slower in 5- and 15-day-old rats. Age differences in absorption from the abdominal cavity or in the reabsorption rate in the kidney tubules can be excluded. The excretion of furosemide by the kidney is competitively inhibited by p-aminohippuric acid (PAH). The relative small inhibitory effect of PAH in young rats is caused by a smaller participation of tubular secretion in the renal excretion of furosemide in this age group. The half life time of furosemide is 83 min in 5-day-old rats and 47 min in 55-day-old rats. The distribution volume is 146% of body weight in both age groups. The concentration of furosemide in the kidney homogenate is higher in young rats than in adults. The slow renal excretion of furosemide in young rats is in accordance with the prolonged efficacy. The greater efficacy of furosemide in 5- and 15-day-old rats than in adults is caused particularly by differences in the conditions for diuretic effectiveness, especially by the retention of water and electrolytes in young rats.

Absorption↗

PubMed1992

Plasma concentration of furosemide versus specific gravity of urine in predicting dose of administration in race horses.

This study was undertaken to determine the applicability of plasma concentration of furosemide and specific gravity (SG) of urine in regulating the use of furosemide administered 4 hours prior to race time in Exercise-Induced Pulmonary Hemorrhage (EIPH) race horses. Nonbleeders (CTL) and certified bleeders (FUR) actively racing in Illinois (IL) and Pennsylvania (PA) were used in the study. Various doses (less than 250, 250, 300, 350, 400 and 500 mg) were administered either as a single intravenous (IV) dose or as a combination (IV-IM) of IV and intramuscular (IM) administrations 4 hours before race time. Plasma and urine samples were obtained post race for determination of furosemide concentration in plasma and measurement of SG of the urine in both CTL and FUR groups. Plasma samples were analyzed for furosemide using High Performance Liquid Chromatography with Fluorescence Detection. SG was measured using a digital refractometer. The results indicate a significant difference (p less than 0.0001) in the SG of the urine samples between the CTL and FUR groups irrespective of the route of administration (IV versus IV-IM). However, SG values of the urine in some CTL samples were lower than those in some FUR samples and vice versa. Thus, the use of SG alone is not reliable for predicting either the dose or the administration of furosemide to race horses. The plasma concentrations of furosemide following the administration (IV) of 250 mg or 500 mg 4 hours prior to race time were indistinguishable (25.91 +/- 4.45 versus 28.12 +/- 6.99 ng/ml, respectively); the majority of the horses in the groups had a plasma concentration of less than 40 ng/ml. When taken in total, plasma concentration of furosemide can only be used as a guide in regulating the administration of furosemide to race horses.

Animals↗

PubMed2003

Detection, quantification, and pharmacokinetics of furosemide and its effects on urinary specific gravity following IV administration to horses.

Furosemide is a potent loop diuretic used for the prevention of exercise-induced pulmonary hemorrhage in horses. This drug may interfere with the detection of other substances by reducing urinary concentrations, so its use is strictly regulated. The regulation of furosemide in many racing jurisdictions is based on paired limits of urinary SG (<1.010) and serum furosemide concentrations (>100 ng/ml). To validate this regulatory mechanism, a liquid chromatography/mass spectrometry/mass spectrometry method employing a solid-phase extraction procedure and furosemide-d5 as an internal standard was developed. The method was used to determine the pharmacokinetic parameters of furosemide in equine serum samples and its effects on urinary SG after IV administration (250 mg) to 10 horses. Pharmacokinetic analysis showed that serum concentrations of furosemide were well described by a two-compartmental open model. Based on results in this study, it is very unlikely for horses to have serum furosemide concentrations greater than 100 ng/ml or urine SG less than 1.010 at 4 hours after administration (250 mg IV). However, it should be remembered that urine SG is a highly variable measurement in horses, and even without furosemide administration, some horses might naturally have urine SG values less than 1.010.

Animals↗