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PubMedDate not supplied

[Effect of intraperitoneal furosemide administration on levels of +proteins+ in plasma and signs of their ability to be dialyzed during intermittent peritoneal dialysis].

The study aimed at evaluating an effect of intraperitoneal furosemide on plasma proteins such as albumins, globulins, IgG and IgA and their loss during dialysis. An experiment involved 18 patients with critical renal failure treated with intermittent peritoneal dialyses. Furosemide was administered intraperitoneally with dialysing fluid (40 mg/1) in a total dose of 240 mg. Each patient underwent 2 dialyses of 14 exchanges each. The first dialysis without furosemide served as a control of plasma protein loss during conventional dialysis with a fluid of 369 mOsm/kg at flow rate 2.4 l/hour. Furosemide was given during the second dialysis during three consecutive exchanges. An effect of furosemide on plasma proteins was compared with the results obtained before and after its administration. It was found that furosemide did not change plasma proteins levels and does not increase their loss during exchanges of dialysing fluid containing this drug; during dialysing fluid exchanges without furosemide some indices of IgG and IgA dialysis are significantly decreased due to an increase in ultrafiltration following furosemide cessation. It is important for the increase in intermittent peritoneal dialyses efficiency with the aid of furosemide that its short-term administration does not increase proteins loss during dialysis, if their molecular weight is not exceeding 69,000.

Adult↗

PubMed1990

Effects of furosemide on the racing times of Thoroughbreds.

The effects of furosemide on the racing times of 79 horses without exercise-induced pulmonary hemorrhage (EIPH) and 52 horses with EIPH were investigated. Racing times were adjusted to 1-mile equivalent racing times by 2 speed handicapping methods, and analysis of covariance was used to adjust actual racing times by winning time and distance for each race. All 3 methods of determining racing time indicated that geldings without EIPH had significantly faster racing times (P less than 0.05) when given furosemide before racing than when furosemide was not given before racing. Females and colts without EIPH were determined to have faster racing times when furosemide was given before racing, but the difference was not significant. Geldings with EIPH had significantly faster racing times (P = 0.0231) when given furosemide before racing, as determined by one of the speed handicapping methods. There was a strong correlation (range 0.9314 to 0.9751) between the 1-mile equivalent racing times, as determined by the 2 speed handicapping methods for horses with and without EIPH. Furosemide failed to prevent the development of EIPH in many horses that were previously considered to be EIPH-negative. When given furosemide, 62 (25.3%) of 235 EIPH-negative horses were EIPH-positive after racing. Furosemide had questionable efficacy for prevention of EIPH in known EIPH-positive horses. Thirty-two (61.5%) of 52 EIPH-positive horses given furosemide before a race remained EIPH-positive after that race.

Animals↗

PubMed1989

Role of medullary plasma flow in the attenuated furosemide response in indomethacin-treated rats.

To determine the role of medullary hemodynamics in the attenuated furosemide response observed during prostaglandin synthesis inhibition, medullary plasma flow was measured by the albumin accumulation technique in nondiuretic rats and during furosemide administration (4 mg/kg b.wt./hr) in indomethacin- or indomethacin vehicle-treated rats. As in previous studies indomethacin attenuated furosemide chloruresis (FeCl: 11.4 +/- 1.1 vs. 5.0 +/- 0.9%, P less than .001) without altering mean arterial pressure, inulin clearance or total renal blood flow. Medullary plasma flow was not different between nondiuretic rats and furosemide-treated rats (41.4 +/- 4.3 vs. 41.3 +/- 3.4 ml/min/100 g of tissue). Medullary plasma flow was reduced (P less than .05) during indomethacin antagonism of furosemide chloruresis (41.3 +/- 3.4 vs. 29.1 +/- 2.8 ml/min/100 g of tissue). Angiotensin II blockade with saralasin (2 micrograms/kg/min) prevented the fall in medullary plasma flow in indomethacin-treated rats during furosemide infusion but did not alter mean arterial pressure, inulin clearance or total renal blood flow. However, furosemide's chloruretic response in rats treated with both indomethacin and saralasin remained lower (P less than .001) than that in vehicle-treated rats (FeCl 4.7 +/- .94 vs. 11.4 +/- 1.1%) and was not different from that in indomethacin-treated rats. These data demonstrate that although medullary plasma flow is reduced during indomethacin antagonism of furosemide response this change does not contribute to the attenuated chloruresis. Additionally, the dissociation of the antichloruretic and hemodynamic effects of indomethacin observed during saralasin administration suggest that hemodynamic mechanisms are not involved in the attenuated response to furosemide observed during prostaglandin synthesis inhibition.

Animals↗

PubMed1986

Competition of organic anions for furosemide and p-aminohippurate secretion in the rabbit.

The excretion of [14C]- or [35S]furosemide and [3H]-p-aminohippurate (PAH) injected within 4 min into the left renal artery of rabbits was measured under brisk mannitol diuresis. The estimated rate of furosemide secretion during the first pass through the left kidney was lower than that of PAH when neither of the two transport processes were saturated: 7.9 and 12.9% of the total amounts injected were secreted per minute, respectively. Different competitive inhibitors were injected i.v. Probenecid (50 mg/kg) inhibited furosemide and PAH secretion by 95 and 80%, respectively. Pyrazinoate at plasma concentrations of 3 to 5 mM had no effect on either anion. Indomethacin (10 mg/kg) depressed furosemide secretion by 24% but had no effect on PAH secretion. PAH at a concentration of 9 to 17 mM in plasma depressed furosemide secretion by only 44 to 66%. Furosemide did not inhibit PAH secretion when infused into the left renal artery at a rate 5000 times higher than PAH. It was concluded that furosemide is secreted partly by the transport system secreting PAH, for which it had only a low affinity, and partly by a transport system for which indomethacin had some affinity. This latter transport system, in turn, differs from that secreting pyrazinoate. The furosemide-induced natriuresis, in both kidneys, was proportional to the urinary excretion rate of furosemide until the fractional excretion of Na+ reached an apparent maximum of 20 to 30%.

Aminohippuric Acids↗

PubMed1986

Clearance of furosemide by the gastrointestinal tract.

Approximately 45% of i.v. administered furosemide is eliminated by nonrenal clearance mechanisms. Indirect evidence suggests this might represent intestinal secretion. Therefore, we examined whether the intestinal tract serves as a drug-eliminating organ in man. Intestinal perfusion studies were performed in six healthy volunteers during i.v. furosemide administration (mean serum concentration, 3.74 +/- 0.64 microgram/ml). Subjects were intubated with a multilumen tube which allowed examination of transmucosal water, solute and furosemide movement at separate levels of the gastrointestinal tract. A poorly absorbable electrolyte-mannitol solution was infused in the jejunum (15 ml/min), with polyethylene glycol as a nonabsorbable marker. Furosemide elimination occurred at an equally low rate in all areas of the intestinal tract. Furosemide clearance for the total gastrointestinal tract was 2.1 +/- 0.4 ml/min (mean +/- S.E.M.) compared to a renal clearance of 93.1 +/- 4.6 ml/min. Thus, gastrointestinal elimination amounted to only 2% of renal elimination. The luminal concentration of furosemide in the intestinal tract did not exceed a mean of 0.5 microgram/ml. When the experiments were repeated after administration of probenecid, gut clearance was unchanged but renal clearance was reduced by 70%. In the ileum, furosemide enhanced bicarbonate secretion and induced chloride absorption. We conclude that the intestinal tract contributes only minimally to furosemide elimination in man. From concentration gradients between lumen and plasma and from the fact that probenecid had no effect on elimination rate, it appears likely that active secretion into the intestinal lumen does not occur and that all furosemide appearance in the gut results from passive diffusion.

Adolescent↗

PubMed1985

Compatibility of furosemide with aminoglycoside admixtures.

The compatibility of furosemide with i.v. admixtures containing each of five different aminoglycosides was studied. Admixtures of amikacin 2 mg/ml, gentamicin 1.6 mg/ml, kanamycin 2 mg/ml, netilmicin 1.5 mg/ml, and tobramycin 1.6 mg/ml (as the sulfate salts) were prepared in both 5% dextrose injection and 0.9% sodium chloride injection in minibags. Furosemide injection 4 ml (40 mg) was then added to each admixture, and the admixtures were examined visually and microscopically for precipitate. The macroscopic and microscopic evaluations were repeated 15 minutes and 24 hours after mixing. To simulate Y-site injection of furosemide, furosemide injection 1 ml (10 mg) was added to 1 ml of each aminoglycoside admixture in a syringe. For admixtures in which precipitates formed, the pH was recorded before and after adding furosemide to subsequent admixtures and also after dropwise addition of 1N sodium hydroxide until the precipitate dissolved. Precipitates were identified using spectrophotometric analysis and melting point determinations. Addition of furosemide resulted in a precipitate only in admixtures containing gentamicin sulfate or netilmicin sulfate; the results for the simulated Y-site injection study were the same. Spectrophotometric analysis and melting point determinations revealed that the precipitate was furosemide. Because furosemide precipitates when added to admixtures containing either gentamicin sulfate or netilmicin sulfate in 5% dextrose injection or 0.9% sodium chloride injection, furosemide should be administered separately or the i.v. tubing should be flushed thoroughly before and after administering this drug via a Y-injection site.

Amikacin↗

PubMed1983

Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites. Relationship between the diuretic response and the activity of the renin-aldosterone system.

Loop and distal diuretics are the basic drugs for the treatment of ascites. Although pharmacologic studies indicate that the natriuretic potency of loop diuretics is much greater than that of distal diuretics, there are no studies comparing the efficacy of these drugs in cirrhosis. Forty nonazotemic cirrhotic patients with ascites and avid sodium retention were randomly allocated into two groups. Group 1 contained 21 patients treated with furosemide; group 2 contained 19 patients treated with spironolactone. The initial doses were 80 and 150 mg/day, respectively. These doses were increased to 160 and 300 mg/day, respectively, if there was no response. Cases not responding to furosemide and spironolactone were later treated with spironolactone and furosemide, respectively. In group 1, 11 of the 21 patients responded to furosemide, while in group 2, 18 of the 19 patients responded to spironolactone (p less than 0.01). Of the 10 patients in group 1 not responding to furosemide, 9 responded later to spironolactone. The diuretic response to furosemide and spironolactone was related to the activity of the renin-aldosterone system. Patients with higher renin and aldosterone did not respond to furosemide and required 300 mg/day of spironolactone to achieve a diuretic response. These results indicate that (a) at the dosages used in the study, spironolactone is more effective than furosemide in nonazotemic cirrhosis with ascites, and (b) the activity of the renin-aldosterone system influences the diuretic response to furosemide and spironolactone in these patients.

Ascites↗

PubMed1984

Probenecid reduces cochlear effects and perilymph penetration of furosemide in chinchilla.

Previous investigation has suggested that the ototoxicity of furosemide is related to penetration of the drug into the inner ear and that active drug transport out of the inner ear may be responsible for maintaining the serum-perilymph drug concentration gradient. We further tested this hypothesis by investigating the endocochlear potential (ototoxicity) and furosemide perilymph concentrations after furosemide administration to chinchillas pretreated with the organic anion transport inhibitor, probenecid. Probenecid pretreatment attenuated the fall in endocochlear potential seen after furosemide (25 mg/kg i.v.): untreated, 58.6 +/- 27.0 mV; probenecid pretreatment, 14.1 +/- 11.9 mV (P less than .01). Furosemide concentrations in perilymph were correspondingly lower after probenecid (P less than .003), although serum furosemide concentrations were not affected by probenecid pretreatment. Diuresis, measured over an 8-hr period after furosemide, was also uneffected by probenecid. These results confirm the proposed relationship between inner ear furosemide concentrations and the occurrence of ototoxicity due to this drug. However, the determinants of penetration of this drug into the inner ear are unclear. The observation that probenecid pretreatment attenuates the ototoxic effect of furosemide while the diuretic effect is preserved suggests this drug combination warrants further investigation.

Animals↗

PubMed1981

The role of volume depletion, antidiuretic hormone and angiotensin II in the furosemide-induced decrease in mesenteric conductance in the dog.

Furosemide caused a significant reduction in mesenteric blood flow and conductance as early as 10 min after administration. When fluid losses were not replaced, conductance continued to decline. In volume-repleted animals, conductance fell initially but failed to decrease further. Thus, furosemide decreases mesenteric conductance in two ways: a small early decrease which is not related to volume loss and a later more marked decrease which is related to volume loss. The initial decrease in conductance seen in furosemide-treated animals appears to be mediated via the renin-angiotensin system. In volume-repleted as well as volume-depleted animals, the plasma concentrations of renin and angiotensin II, but not antidiuretic hormone, were increased 10 min after furosemide administration. Also, inhibitors of the renin-angiotensin system abolished the response. The later decrease in mesenteric conductance induced by furosemide is more complex. When fluid losses were not replaced, plasma levels of angiotensin II and renin, as well as antidiuretic hormone, were increased 40 min after furosemide administration. Neither an infusion of Sar1-Ile8-angiotensin II nor hypophysectomy, alone, prevented the furosemide-induced decrease in conductance. The decrease in conductance was reversed when Sar1-Ile8-angiotensin II was infused into hypophysectomized dogs. Thus, the later more marked decrease in conductance induced by furosemide is related to three factors: volume loss, plasma concentration of angiotensin II and plasma concentration of antidiuretic hormone. Mesenteric conductance is decreased by furosemide if plasma concentrations of one or both vasoactive factor are elevated in the presence of a decrease in extracellular volume.

1-Sarcosine-8-Isoleucine Angiotensin II↗

PubMed1995

Pharmacologic interaction of furosemide and phenylbutazone in horses.

The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg, PO, at 24 hours and 4.4 mg/kg, IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration significantly attenuated, but did not abolish, the diuretic effect of furosemide. Phenylbutazone completely inhibited the immediate effect of furosemide on cardiac output, stroke volume, total peripheral resistance, and right ventricular peak pressure. Premedication with phenylbutazone did not inhibit equally the diuretic and hemodynamic effects of furosemide, indicating that some of furosemide's hemodynamic effects are mediated by an extrarenal activity of furosemide.

Analysis of Variance↗

PubMed1995

Effect of inhaled furosemide on lung clearance of technetium-99m-DTPA.

UNLABELLED: The diuretic furosemide has been reported to have a protective effect on allergic asthmatic reactions. This study was performed to investigate the effect of aerosolized furosemide on the lung clearance of 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA). METHODS: Pulmonary clearance rates of 99mTc-DTPA were measured by a computerized gamma camera with and without the inhalation of aerosol furosemide in 6 nonsmoking normal volunteers (Group 1), 7 smokers without pulmonary disease (Group 2) and 11 patients with asthma (Group 3). RESULTS: None of the six normal volunteers showed significant effects of inhaled furosemide on the 99mTc-DTPA clearance rates. Three of seven smokers presented an accelerated 99mTc-DTPA clearance by inhaled furosemide and the other four showed no significant change of 99mTc-DTPA clearance by furosemide inhalation. However, in 10 of 11 patients with asthma, there was significant suppression of 99mTc-DTPA clearance by furosemide inhalation. CONCLUSION: Asthmatics possess a furosemide-sensitive mechanism. Pulmonary aerosol scintigraphy with 99mTc-DTPA will be useful in predicting the effect of inhaled furosemide therapy.

Administration, Inhalation↗

PubMed1994

Selective pulmonary and venous smooth muscle relaxation by furosemide: a comparison with morphine.

Furosemide and morphine reduce pulmonary edema associated with congestive heart failure. It is uncertain whether furosemide or morphine are direct-acting relaxants of arterial and venous smooth muscle. The authors compared the effect of furosemide and morphine on isolated rings of canine pulmonary artery (PA) and vein (PV) and mesenteric, splenic and anterior tibial arteries and their corresponding veins precontracted with norepinephrine or (15S)-hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid. Furosemide (10-300 microM) selectively relaxed veins by an endothelium-independent mechanism, with its greatest efficacy on the PV. Morphine (10-1000 microM) relaxed both arteries and veins. The mechanism of relaxation by furosemide and morphine was examined in the PV and PA. Morphine-induced relaxation of the PV and PA was dependent on prostanoid release from endothelium and smooth muscle because it was attenuated in endothelium-rubbed and ibuprofen-treated PV and PA but not in blood vessels treated with inhibitors of nitric oxide system/cyclic GMP system (I-NG-nitroarginine and methylene blue). Furosemide-mediated relaxation of the PV was refractory to each of these interventions. Similarly, furosemide- and morphine-induced relaxation of the PV were unaffected by 4-aminopyridine, tetraethylammonium, glibenclamide, dendrodotoxin and apamin and, thereby, were independent of an action on K+ channels. Reduction of extracellular K+ or Cl- attenuated furosemide-mediated relaxation of, and inhibition of 86Rb+ uptake by, PV even in the presence of ouabain. It was concluded that furosemide relaxes veins by an effect on Na+/K+/Cl- cotransport or chloride-mediated refilling of intracellular calcium stores.

Animals↗

PubMed1976

The effect of prophylactic use of furosemide on renal function during open heart surgery.

Forty-five patients who underwent open heart surgery were divided into a short-perfusion group (SPG, 21 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 and postoperatively all patients were given furosemide when necessary, i.e. when the volume for diuresis per hour declined below 40 ml/h. The patients who received prophylactic furosemide in the LPG subsequently had clearly less need for furosemide (3.9 mg/h) than the control subjects (7.9 mg/h/3 day). The patients with furosemide prophylaxis in the LPG had significantly ( less than 0.05) higher creatinine clearance and lower serum creatinine values during the postoperative night period and on the 3rd day. In perfusions lasting less than 60 minutes the patients with furosemide prophylaxis had significantly higher urine flow (p less than 0.001), sodium excretion (p less than 0.001) and potassium excretio-n (p less than 0.01) during bypass surgery and postoperatively compared with that of controls. According to our findings, the prophylactic use of furosemide had a beneficial effect on glomerular filtration rate (endogenous creatinine clearance) and postoperative serum creatinine level in LPG. In perfusion shorter than 60 minutes furosemide prophylaxis may be harmful owing to the increased excretion of water, sodium and potassium.

Acute Kidney Injury↗

PubMedDate not supplied

Dose-dependent evaluation of the effects of nebulized furosemide on pulmonary function in ventilated preterm infants.

OBJECTIVE: We have previously shown that a single dose of nebulized furosemide improves tidal volume and pulmonary compliance for up to a 2-hour study period. This study is undertaken in order to find out (a) whether increasing the dose of nebulized furosemide from 1 to 2 mg/kg of body weight will further improve the pulmonary mechanics in premature infants with evolving chronic lung disease and (b) whether the effects of a single dose of nebulized furosemide last beyond 2 hours. STUDY DESIGN: The effect of nebulized furosemide on pulmonary mechanics was studied at a mean postnatal age of 24 days (range 14 to 50 days) in 13 premature infants, 24 to 28 weeks' gestational age, who had been dependent on mechanical ventilation since birth. Furosemide was administered by nebulization at doses of 1 and 2 mg/kg of body weight, in random order, on two separate days 24 hours apart. Pulmonary function studies were performed before and 2, 4, and 6 hours after the nebulization. Urine was collected for 6 hours immediately before and for 6 hours after the nebulization. RESULTS: Furosemide by nebulization at 1 and 2 mg/kg of body weight resulted in significant improvement in tidal volume and compliance. There was no difference in the magnitude of response between the two doses. Neither 1 nor 2 mg/kg of body weight of nebulized furosemide had any effect on airway resistance. The improvement was maximum for up to 4 hours and lasted for up to 6 hours after the nebulization and was not associated with diuresis or increased excretion of urinary electrolytes. CONCLUSION: A single dose of nebulized furosemide improves pulmonary function for up to 6 hours after its administration. Increasing the dose from 1 to 2 mg/kg of body weight results in no further improvement in the pulmonary function. The pulmonary effects of nebulized furosemide are independent of its diuretic action.

Aerosols↗

PubMed1976

Metabolic activation of furosemide to a chemically reactive, hepatotoxic metabolite.

The possibility that furosemide-induced hepatic necrosis results from the formation of a chemically reactive hepatotoxic metabolite has been examined. Hepatotoxic doses of 3H-furosemide or 14C-furosemide were administered to normal mice and to mice pretreated with piperonyl butoxide, cobalt chloride, alpha-naphthylisothiocyanate or phenobarbital. Mice were killed at various time intervals and tissues were examined for necrosis, for free furosemide concentrations and for covalently bound metabolites of furosemide. Little furosemide was covalently bound to muscle, whereas the amount of covalently bound material in liver usually paralleled the severity of live necrosis after alteration by the pretreatments. The severity of hepatic necrosis failed to correlate with furosemide concentrations in liver or plasma. Furosemide was shown to be metabolically activated to an arylating intermediate by a cytochrome P-450 mixed function oxidase in hepatic microsomes. Additional experiments demonstrated that the furan ring of furosemide was the portion activated.

Alanine Transaminase↗

PubMed1989

Direct effects of furosemide and amiloride on the perfused and ischaemic rat heart.

The present study was undertaken in order to assess direct effects of furosemide and furosemide plus amiloride upon the perfused and ischaemic isolated rat heart. Furosemide in concentrations ranging between 4-400 mg/l in the perfusate increased coronary flow in a concentration dependent manner. There was no evidence for a negative inotropic effect of furosemide. However, very high doses of furosemide (400 mg/l) decreased the post-ischaemic values of left ventricular developed pressure, coronary flow rate, adenosine triphosphate, creatine phosphate and potassium, and increased the myocardial content of calcium and sodium. Furosemide 4 mg/l and 40 mg/l had no effect on post-ischaemic parameters compared to the control group except that furosemide 40 mg/l increased the recovery of coronary flow. Although amiloride 13.3 mg/l alone did not affect post-ischaemic recovery, the addition of this dose to furosemide 400 mg/l improved the post-ischaemic recovery of left ventricular developed pressure, coronary flow rate and adenosine triphosphate. The myocardial content of magnesium and potassium was higher indicating protection of amiloride by its magnesium- and potassium-sparing properties opposing ischaemic losses aggravated by the exposure to furosemide.

Animals↗

PubMed1977

Effects of probenecid on furosemide kinetics and natriuresis in man.

Furosemide kinetics were studied in 4 normal subjects after single intravenous injections (1 mg/kg). One experiment was done after pretreatment with probenecid. The apparent volume of furosemide distribution was unchanged after probenecid (10.9 L). The mean plasma clearance fell from 155 to 85 ml/min and the mean plasma t1/2 rose from 36 to 61 min. Renal clearance of furosemide fell below 50% of control after probenecid, but the kidney remained the main route of its excretion (75% of the dose appeared in the urine). In another experiment in 4 subjects an infusion of furosemide was sustained following a loading dose to maintain a constant plasma level. After a control period, probenecid was given orally. This resulted in a decrease in renal excretion of furosemide with a simultaneous rise in its plasma concentration. Despite the rising plasma furosemide concentration, however, there was a diminution in both urine flow and the excreted fraction of filtered sodium, which suggested some reduction of diuretic action. In doses commonly used, probenecid reduces renal elimination of furosemide in man with only a mild impairment of its diuretic activity. This suggests that furosemide is eliminated predominantly by way of proximal tubular secretion and that tubular rather than plasma concentration is the main determinant of its diuretic effect.

Drug Interactions↗

PubMed1977

Influence of probenecid and spironolactone on furosemide kinetics and dynamics in man.

The pharmacokinetics and pharmacodynamics following administration of furosemide (40 mg intravenously) have been studied before and after treatment with probenecid (0.5 gm orally every 6 hr for 3 days) and spironolactone (200-mg initial oral dose followed by 50 mg every 6 hr for 3 days) in 6 normal male subjects. Urine losses during each study period were replaced with saline-dextrose-KCl intravenously. The study was performed with the use of a Latin-square design. Probenecid pretreatment induced significant reductions in renal clearance of furosemide by 78%, the extrarenal clearance by 56%, and the volume of distribution by 52%. As a consequence, furosemide half-life was increased by 54%. Probenecid significantly reduced the rate of sodium excretion at all plasma concentrations of furosemide, but the ratio between urinary furosemide concentration and urinary sodium concentration was not altered. Since the proportion of furosemide excreted unchanged in the urine was not markedly changed, total diuretic response was not influenced by probenecid. There was no evidence of any pharmacokinetic interaction between spironolactone and furosemide. The relationship of furosemide kinetics to dynamics observed in these studies confirms that, in man, the diuretic response is determined by drug that reaches the renal tubule rather than the drug level in plasma.

Adult↗