Na+/2Cl-/K+ (NKCC) symporter; NKCC1/2; GABAA receptors

The poorly differentiated human gastric cancer cell line MKN45 exhibits a considerable change in proliferation rate when exposed to furosemide (500 µM) over 72-96 hours. On the other hand, MKN28 cells—a cell line of human gastric adenocarcinoma that is moderately differentiated—were unaffected. Compared to MKN28 cells, MKN45 cells develop at a faster pace [4]. In healthy people's erythrocytes, furosemide (10 µM, 30 µM, and 100 µM; 45 min exposure) dramatically lowers [Ca(2+)](i) and cation channel activity. Similar effects were seen by tert-butyl hydroperoxide on non-selective cation channel activity, [Ca(2+)](i), and cell membrane disruption; however, furosemide considerably reduced these effects as well [5].

To create a deaf mouse model, kanamycin (KM) (1000 mg/kg) and furosemide (ip; 100 mg/kg; single dose) were injected into C57BL/6 mice. On days 1, 2, and 3, following injection, hearing loss and cochlear hair cell destruction were measured, accordingly. Day 3 of the animals showed abnormal OHC (outer hair cells) morphology of the top, middle, and bottom turns, and hearing had already severely declined since day 2 (day 1 group) [3].

GABAA receptors in cerebellar granule cells are unique in expressing a subtype containing the alpha6 subunit. This receptor subtype has high affinity for GABA and produces a degree of tonic inhibition on cerebellar granule cells, modulating the firing of these cells via spillover of GABA from GABAergic synapses. This receptor subtype also has selective affinity for the diuretic furosemide over receptors containing other alpha-subunits. Furosemide exhibits approximately 100-fold selectivity for alpha6-containing receptors over alpha1-containing receptors. By making alpha1/alpha6 chimeras we have identified a transmembrane region (209-279) responsible for the high furosemide sensitivity of alpha6beta3gamma2s receptors. Within the alpha1 transmembrane region, a single amino acid was identified that when mutated from threonine to isoleucine, increased furosemide sensitivity by 20-fold. We demonstrate the beta-subunit selectivity of furosemide to be due to asparagine 265 in the beta2 and beta3 transmembrane-domain II similar to that observed with potentiation by the anticonvulsant loreclezole. We also show that Ile in transmembrane-domain I accounts for the increased GABA sensitivity observed at alpha6beta3gamma2s compared with alpha1beta3gamma2s receptors, but did not affect direct activation by pentobarbital or potentiation by the benzodiazepine flunitrazepam. Location of these residues within transmembrane domains leads to speculation that they may be involved in the channel-gating mechanism conferring increased receptor activation by GABA, in addition to conferring furosemide sensitivity.[2]

Furosemide, a blocker of Na(+)/K(+)/2Cl(-) cotransporter (NKCC), is often used as a diuretic to improve edema, ascites, and pleural effusion of patients with cancers. The aim of the present study was to investigate whether an NKCC blocker affects cancer cell growth. If so, we would clarify the mechanism of this action. We found that poorly differentiated gastric adenocarcinoma cells (MKN45) expressed the mRNA of NKCC1 three times higher than moderately differentiated ones (MKN28) and that the NKCC in MKN45 showed higher activity than that in MKN28. A cell proliferation assay indicates that furosemide significantly inhibited cell growth in MKN45 cells, but not in MKN28 cells. Using flow cytometrical analysis, we found that the exposure to furosemide brought MKN45 cells to spend more time at the G(0)/G(1) phase, but not MKN28 cells. Based on these observations, we indicate that furosemide diminishes cell growth by delaying the G(1)-S phase progression in poorly differentiated gastric adenocarcinoma cells, which show high expression and activity of NKCC, but not in moderately differentiated gastric adenocarcinoma cells with low expression and NKCC activity.[1]

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Background: Furosemide, a loop diuretic inhibiting the renal tubular Na(+),K(+),2Cl(-) cotransporter, has been shown to decrease cytosolic Ca(2+) concentration ([Ca(2+)](i)) in platelets and erythrocytes. [Ca(2+)](i) in erythrocytes is a function of Ca(2+) permeable cation channels. Activation of those channels e.g. by energy depletion or oxidative stress leads to increase of [Ca(2+)](i), which in turn triggers eryptosis, a suicidal erythrocyte death characterized by cell membrane scrambling. The present study was performed to explore whether furosemide influences the cation channels and thus influences eryptosis.[5]
Methods: Cation channel activity was determined by whole-cell patch clamp, [Ca(2+)](i) utilizing Fluo3 fluorescence and annexin V binding to estimate cell membrane scrambling with phosphatidylserine exposure. [5]
Results: A 45 min exposure to furosemide (10 and 100 µM) slightly, but significantly decreased cation channel activity and [Ca(2+)](i) in human erythrocytes drawn from healthy individuals. ATP-depletion (> 3 hours, +37°C, 6 mM ionosine and 6 mM iodoacetic acid) enhanced the non-selective cation channel activity, increased [Ca(2+)](i) and triggered cell membrane scrambling, effects significantly blunted by furosemide (10 - 100 µM). Oxidative stress by exposure to tert-butylhydroperoxide (0.1 -1 mM) similarly enhanced the non-selective cation channels activity, increased [Ca(2+)](i) and triggered cell membrane scrambling, effects again significantly blunted by furosemide (10 - 100 µM).[5]
Conclusions: The present study shows for the first time that the loop diuretic furosemide applied at micromolar concentrations (10 - 100 µM) inhibits non-selective cation channel activity in and eryptosis of human erythrocytes.[5]

Deaf Mouse Model and Study Groups[3]
A deaf mouse model (C57BL/6 mouse, 4–6 weeks of age, weight of 15–25 g) was created by intraperitoneal injection of KM (1000 mg/kg) followed by furosemide (100 mg/kg) within 30 min. In Experiment 1, to assess the initial temporal change of hearing and the extent of hair cell damage in this deaf mouse model, total nine mice were divided into three groups: Day-1 (N = 3), Day-2 (N = 3) and Day-3 (N = 3). After injection of KM and furosemide on day 0, hearing loss and cochlear hair cell damage were evaluated on day 1, day 2 and day 3, respectively (Supplementary file S1).[3]
In Experiment 2, to test the rescue effect of GV1001, total 120 mice were divided into the following three treatment groups: GV1001 (N = 40), dexamethasone (N = 40) and saline (N = 40). GV1001 (10 mg/kg), dexamethasone (15 mg/kg), or saline was subcutaneously administered for three consecutive days after the injection of KM and furosemide. To compare the rescue effect of GV1001 on different time points, each group was divided into four subgroups according to the time points of GV1001, dexamethasone, and saline treatment: D0 group (days 0, 1 and 2), D1 group (days 1, 2 and 3), D3 group (days 3, 4 and 5), and D7 group (days 7, 8 and 9; Supplementary file S2).[3]

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A deaf mouse model was created by intraperitoneal injection of KM and furosemide. First, to test the early temporal change of hearing and extent of hair cell damage after KM and furosemide injection, hearing and outer hair cells (OHCs) morphology were evaluated on day 1, day 2 and day 3 after injection. In the second experiment, following KM and furosemide injection, GV1001, dexamethasone, or saline were given for three consecutive days at different time points: D0 group (days 0, 1, and 2), D1 group (days 1, 2, and 3), D3 group (days 3, 4, and 5) and D7 group (days 7, 8, and 9). The hearing thresholds were measured at 8, 16, and 32 kHz before ototoxic insult, and 7 days and 14 days after KM and furosemide injection. After 14 days, each turn of the cochlea was imaged to evaluate OHCs damage. GV1001-treated mice showed significantly less hearing loss and OHCs damage than the saline control group in the D0, D1 and D3 groups (p < 0.0167). However, there was no hearing restoration or intact hair cell in the D7 group. GV1001 protected against cochlear hair cell damage, and furthermore, delayed administration of GV1001 up to 3 days rescued hair cell damage and hearing loss in KM/furosemide-induced deaf mouse model.[3]

Absorption, Distribution and Excretion
After oral administration, furosemide is absorbed via the gastrointestinal tract. The bioavailability of oral formulations varies considerably, ranging from 10% to 90%. The bioavailability of furosemide in oral tablets and oral solutions is approximately 64% and 60% of that in intravenous administration, respectively. The kidneys are responsible for 85% of the total clearance of furosemide, of which approximately 43% is excreted renally. After intravenous administration, significantly more furosemide is excreted in the urine than in tablets or oral solutions. Approximately 50% of furosemide is excreted unchanged in the urine, with the remainder metabolized in the kidneys to glucuronide. The volume of distribution after intravenous administration of 40 mg furosemide in healthy subjects was 0.181 L/kg, and in patients with heart failure, it was 0.140 L/kg. The plasma clearance after intravenous administration of 400 mg furosemide in patients with heart failure was 1.23 mL/kg/min, and in healthy subjects, it was 2.34 mL/kg/min.
The amount of furosemide excreted in urine after intravenous administration was significantly higher than that after oral tablets or solution. There was no significant difference in the amount of unchanged drug excreted in urine between the two oral formulations.
Higher concentrations of furosemide were detected in both umbilical venous plasma and amniotic fluid in 18 pregnant women on the day of delivery. The ratio of furosemide concentration in maternal venous plasma to umbilical cord plasma increased over time, approaching 1 8–10 hours after administration. The plasma half-life of furosemide in pregnant women appeared to be longer than in non-pregnant healthy volunteers. In one patient, the plasma concentration of furosemide remained stable over a 5-hour observation period.
In a study of patients with normal renal function, approximately 60% of a single oral dose of 80 mg furosemide was absorbed from the gastrointestinal tract. When this dose was administered to fasting adults, the drug appeared in serum within 10 minutes, reached a peak concentration of 2.3 μg/mL within 60–70 minutes, and was almost completely cleared from serum within 4 hours. When taken with food at the same dose, furosemide serum concentrations rise slowly, reaching a peak of approximately 1 μg/mL after 2 hours, and maintaining similar concentrations for 4 hours after administration. However, the diuretic response is similar regardless of whether it is taken with food or on an empty stomach. In another study, the rate and extent of absorption varied considerably when uremic patients orally administered 1 gram of furosemide. The average absorption rate was 76%, and peak plasma concentrations were reached within 2–9 hours (mean 4.4 hours). The serum concentration required to achieve maximum diuresis is unclear, and the extent of the diuretic response has been reported to be unrelated to either peak or average serum concentrations. The diuretic effect of oral furosemide appears within 30 minutes to 1 hour, reaching its maximum in the first or second hour. The duration of action is typically 6–8 hours. The maximum antihypertensive effect may not appear until several days after initiation of furosemide treatment. After intravenous administration of furosemide, the diuretic effect begins within 5 minutes, reaches its maximum within 20–60 minutes, and lasts for approximately 2 hours. Following intramuscular injection, peak plasma concentrations are reached within 30 minutes; the onset of diuresis is slightly later than with intravenous injection. In patients with severely impaired renal function, the diuretic response may be prolonged.
For more complete data on the absorption, distribution, and excretion of furosemide (15 in total), please visit the HSDB records page.

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Metabolism/Metabolites
Furosemide is primarily metabolized by the kidneys, with less metabolism in the liver. The kidneys are responsible for clearing approximately 85% of furosemide, of which approximately 40% involves biotransformation. The two major metabolites of furosemide are the pharmacologically active furosemide glucuronide and salinomycin (CSA) or 4-chloro-5-sulfonamide anthranilic acid.
Furosemide glucuronide appears to be the only, or at least the major, biotransformation metabolite in humans. Some studies have reported the presence of 2-amino-4-chloro-5-sulfonamide anthranilic acid, while others have not; this is considered an artifact arising during analysis. In patients with normal renal function, a small amount of furosemide is metabolized in the liver to the defuranylated derivative 4-chloro-5-sulfonamide anthranilic acid. …

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Biological Half-Life
After oral administration of 40 mg furosemide, the half-life is 4 hours; after intravenous injection, the half-life is 4.5 hours. The terminal half-life of furosemide after parenteral administration is approximately 2 hours. In patients with severe renal failure, the terminal half-life can be prolonged to 24 hours. To investigate the pharmacokinetics of furosemide (Lasix) and its acyl glucuronide and analyze their pharmacodynamic responses, we studied seven healthy subjects with a mean age of 34 years who received a single oral dose of 80 mg furosemide tablets. In plasma, there were two differences in the elimination half-life of furosemide and its conjugates: the half-lives of furosemide were 1.25 hours and 30.4 hours, respectively, and the half-lives of the conjugates were 1.31 hours and 33.2 hours, respectively. ...
In dogs, ...the elimination half-life is approximately 1-1.5 hours.
The elimination half-life of furosemide reported by different researchers varies widely. One study showed that the average elimination half-life after intravenous injection of 20-120 mg of the drug in healthy subjects was approximately 30 minutes. Another study showed that the average elimination half-life after intravenous injection of 1 gram of furosemide in patients with advanced renal failure was 9.7 hours. The elimination half-life was even longer in a patient with concurrent liver disease.
The serum half-life at therapeutic doses is 92 minutes; the serum half-life is prolonged in patients with uremia, congestive heart failure, cirrhosis, as well as in newborns and the elderly. In these patients, the half-life can be extended to 20 hours.

Toxicity Summary
Identification and Uses: Furosemide is a white or slightly yellow solid powder or crystals. Furosemide is used to treat edema caused by a variety of conditions (it can be used alone or in combination with other antihypertensive drugs). Human Studies: Overdose of diuretics is uncommon and rarely results in serious consequences. The most common problems include prolonged overdose, inadequate monitoring, unforeseen drug interactions, or failure to compensate for accompanying hepatic or renal dysfunction. The primary toxic effect is on the kidneys, causing diuresis of water, sodium, and potassium, most commonly resulting in hyponatremia, hypokalemia, and hypochloremic dehydration. Extra caution should be exercised in patients at high risk of renal dysfunction, including those with any kidney disease, diabetes, or borderline fluid and/or electrolyte states. A hospital-based adverse drug reaction study showed an incidence of 21% for furosemide. The most common adverse reactions were hypovolemia, hyperuricemia, and hypokalemia. These adverse reactions were mostly mild, but their incidence and severity increased with increasing daily dose. Hypersensitivity reactions such as rash, photosensitivity, thrombocytopenia, and pancreatitis are rare. An elderly man developed life-threatening hyperkalemia and reversible renal failure after concurrent administration of captopril and furosemide. A 74-year-old man developed acute rhabdomyolysis and myoglobinuria due to hypokalemia after taking furosemide. An adult experienced a severe anaphylactic reaction, manifested as urticaria, angioedema, and hypotension, five minutes after intravenous injection of furosemide. Furosemide abuse (400 mg daily) is associated with severe hyponatremia and central pontine myelinolysis. Self-administered furosemide over a six-year period resulted in renal medullary calcification. Five children developed nephrocalcinosis and kidney stones after furosemide treatment. There are also reports of nephrocalcinosis in premature infants treated with furosemide. Infant gallstones have been caused by furosemide. Tachycardia has been reported after high-dose intravenous administration of furosemide. Renal calcification has occurred in premature infants after furosemide administration. Renal calcification induced by furosemide in low birth weight infants may lead to long-term glomerular and tubular dysfunction. In in vitro experiments, a concentration-dependent increase in the frequency of chromosomal aberrations was observed in human lymphocytes exposed to furosemide for 24 and 72 hours. No such effect was detected in human fibroblast cell lines. Animal studies: Long-term administration to rats can lead to renal tubular degeneration. Renal parenchymal calcification and damage were observed in subchronic studies in dogs. Developmental studies have been conducted in mice, rats, and rabbits. An increased incidence and severity of hydronephrosis (renal pelvis dilation, occasionally including ureteral dilation) was observed in one mouse study and one of three rabbit studies. In male mice intraperitoneally injected with furosemide (0.3–50 mg/kg body weight), a non-dose-dependent increase in the percentage of meiotic cells with chromosomal aberrations was observed throughout the spermatogenesis cycle. Furosemide activity was tested in four Salmonella Typhimurium strains (TA98, TA100, TA1535, and TA1537) at various doses (0, 100, 333, 1000, 3333, and 10,000 μg/plate) with and without metabolic activation. Furosemide was negative in all these tests, and the highest ineffective dose among all tested Salmonella strains was 10,000 μg/plate. It has been reported that furosemide only induces mutations in L5178Y mouse lymphoma cells at the highest tested concentration (1500 μg/mL) in the presence of an exogenous metabolic system. It has also been reported that furosemide, at concentrations of 3750 and 500 μg/mL, can induce sister chromatid exchange and chromosomal aberrations in Chinese hamster CHO cells, with or without an exogenous metabolic system. Furosemide induces chromosomal damage in Chinese hamster lung fibroblasts in vitro, but only in the absence of an exogenous metabolic system. Ecotoxicity studies: Furosemide, when used in combination with other drugs found in wastewater, is genotoxic to zebrafish and toxic to river microbial communities.

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Effects during pregnancy and lactation
◉ Overview of use during lactation
Due to limited information on the use of furosemide during lactation, and the strong diuretic effect of high doses of furosemide which may reduce milk production, alternative medications are preferred, especially when breastfeeding newborns or premature infants. Low-dose furosemide (20 mg daily) does not inhibit lactation.
◉ Effects on breastfed infants
A short-term observation at a medical center found that immediate postpartum use of furosemide by mothers did not have adverse effects on infants.
◉ Effects on Lactation and Breast Milk
Intramuscular injection of furosemide 20 mg on the first postpartum day, followed by oral administration of 40 mg for 4 days, combined with fluid restriction and breast binding, can suppress lactation within 3 days postpartum. The additional effects of furosemide on fluid restriction and breast binding (both of which effectively suppress lactation) are currently unknown. There are currently no data on the effects of loop diuretics on established lactation.
A randomized controlled trial compared the effects of postpartum furosemide (n = 192) versus placebo (n = 192) in women with gestational hypertension and preeclampsia. Patients received either 20 mg of furosemide or placebo for 4 to 5 days. The first dose was taken 6 to 24 hours postpartum, followed by every 24 hours until discharge. There was no difference in breastfeeding difficulties reported between the two groups.
A study of mothers with prenatal hypertension administered 20 mg of furosemide or placebo daily for 5 days postpartum. Mothers reported whether they were exclusively breastfeeding at 2 and 6 weeks postpartum. There was no difference in exclusive breastfeeding rates between the furosemide and placebo groups. Protein Binding: In healthy individuals, protein binding is approximately 91-99% at plasma concentrations ranging from 1 to 400 mcg/mL. At therapeutic concentrations, the free fraction is approximately 2.3-4.1%. Furosemide is primarily bound to serum albumin. Drug Interactions: Methotrexate and other drugs that are significantly secreted by the renal tubules, like furosemide, may reduce the efficacy of furosemide. Conversely, furosemide may reduce the renal clearance of other drugs that are secreted by the renal tubules. Concomitant administration of high doses of furosemide and these drugs may lead to increased serum concentrations of these drugs and may enhance their toxicity, as well as the toxicity of furosemide. Phenytoin Sodium Directly Interferes with the Renal Effects of Furosemide. There is evidence that phenytoin sodium treatment leads to reduced intestinal absorption of furosemide, thereby decreasing peak serum furosemide concentrations.
Furosemide may reduce arterial responsiveness to norepinephrine. However, norepinephrine remains effective.
There is a risk of ototoxicity if cisplatin and furosemide are used concomitantly. Furthermore, if furosemide is used for forced diuresis during cisplatin treatment without reducing the furosemide dose and maintaining positive fluid balance, the nephrotoxicity of nephrotoxic drugs such as cisplatin may be enhanced.
For more complete data on interactions of furosemide (36 in total), please visit the HSDB record page.

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Non-human toxicity values
Oral LD50 in rats (female): 2600 mg/kg
Oral LD50 in rats (male): 2820 mg/kg
Intraperitoneal LD50 in rats: 800 mg/kg
Intravenous LD50 in rats: 800 mg/kg
For more complete data on non-human toxicity values of furosemide (11 in total), please visit the HSDB record page.

[1]. Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family. J Biol Chem. 1996 Jul 5;271(27):16237-44.

[2]. Residues in transmembrane domains I and II determine gamma-aminobutyric acid type AA receptor subtype-selective antagonism by Furosemide sodium. Mol Pharmacol. 1999 Jun;55(6):993-9.

[3]. Novel Peptide Vaccine GV1001 Rescues Hearing in Kanamycin/Furosemide sodium-Treated Mice. Front Cell Neurosci. 2018 Jan 19;12:3.

[4]. Furosemide sodium, a blocker of Na+/K+/2Cl- cotransporter, diminishes proliferation of poorly differentiated human gastric cancer cells by affecting G0/G1 state. J Physiol Sci. 2006 Dec;56(6):401-6.

[5]. Inhibitory effect of Furosemide sodium on non-selective voltage-independent cation channels in human erythrocytes.Cell Physiol Biochem. 2012;30(4):863-75.

Therapeutic Uses

Diuretic; Sodium-potassium chloride cotransporter inhibitor
Oral furosemide can be used to treat hypertension in adults, either alone or in combination with other antihypertensive drugs. In hypertensive patients whose blood pressure is not effectively controlled by thiazide diuretics, furosemide alone may also be ineffective. /US Product Label/
Furosemide is indicated for the treatment of edema associated with congestive heart failure, cirrhosis, and kidney disease (including nephrotic syndrome) in adults and children. Furosemide is particularly useful when a more potent diuretic is required. /US Product Label/
Intravenous furosemide has been shown to be used as adjunctive therapy to treat hypertensive crises, especially in cases of acute pulmonary edema or renal failure. In addition to rapid diuresis, furosemide can enhance the efficacy of other antihypertensive drugs and counteract sodium retention caused by some antihypertensive drugs. /Not included in US Product Label/
For more complete data on the therapeutic uses of furosemide (11 in total), please visit the HSDB record page.

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Drug Warning
/Black Box Warning/ Furosemide is a potent diuretic. Overdose can lead to severe diuresis, causing water and electrolyte loss. Therefore, close medical monitoring is required, and the dosage and dosing regimen must be adjusted according to the individual patient's needs.
Excessive diuresis can lead to dehydration and decreased blood volume, which can result in circulatory failure and may cause vascular thrombosis and embolism, especially in elderly patients. As with any effective diuretic, electrolyte loss may occur during furosemide treatment, especially in patients receiving higher doses and with restricted salt intake. Hypokalemia may occur with furosemide (Lasix), especially with rapid diuresis, insufficient oral electrolyte intake, cirrhosis, or concurrent use of corticosteroids, adrenocorticotropic hormone (ACTH), large doses of licorice, or prolonged use of laxatives. Digitalis treatment may exacerbate the metabolic effects of hypokalemia, particularly on the myocardium. Patients receiving furosemide must be closely monitored for signs of hypovolemia, hyponatremia, hypokalemia, hypocalcemia, hypochloremia, and hypomagnesemia. Patients should be informed of the signs and symptoms of electrolyte disturbances and instructed to seek immediate medical attention if they experience weakness, dizziness, fatigue, syncope, confusion, weakness, muscle cramps, headache, paresthesia, thirst, anorexia, nausea, and/or vomiting. Excessive fluid and electrolyte loss can be minimized by starting with a small dose, carefully adjusting the dose, using intermittent dosing whenever possible, and monitoring the patient's weight. To prevent hyponatremia and hypochloremia, most patients may appropriately increase their sodium intake; however, patients with cirrhosis usually require at least moderate sodium restriction during diuretic therapy. Serum electrolyte, blood urea nitrogen, and carbon dioxide levels should be monitored early in furosemide treatment and periodically thereafter. If excessive diuresis and/or electrolyte disturbances occur, the drug should be discontinued or the dose reduced until homeostasis is restored. Appropriate measures should be taken to correct electrolyte abnormalities.
Frosemide should be used with caution in patients with cirrhosis, as rapid changes in fluid and electrolyte balance may induce hepatic coma or coma.
For more complete (29) drug warnings for furosemide, please visit the HSDB record page.

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Pharmacodynamics
Frosemide is used to treat hypertension and edema associated with congestive heart failure, cirrhosis, and kidney disease (including nephrotic syndrome). Furosemide is a potent loop diuretic that increases renal excretion of sodium and water by inhibiting the reabsorption of sodium and water in the proximal tubule, distal tubule, and loop of Henle. It acts directly on nephron cells and indirectly alters the composition of glomerular filtrate. Furosemide ultimately works by increasing renal urine output. Protein-bound furosemide is transported to the site of action in the kidney and actively excreted via nonspecific organic transporters expressed on the luminal side of the renal tubules. After oral administration, the diuretic effect begins approximately 1 to 1.5 hours later and reaches its peak within 2 hours. The duration of action after oral administration is approximately 4 to 6 hours, but can be as long as 8 hours. After intravenous injection, the effect begins within 5 minutes and reaches its peak within 30 minutes. The duration of action after intravenous injection is approximately 2 hours. The onset of action is slightly delayed after intramuscular injection.

C12H11CLN2O5S

330.74

330.007

C, 43.58; H, 3.35; Cl, 10.72; N, 8.47; O, 24.19; S, 9.69

54-31-9

Furosemide sodium;41733-55-5;Furosemide-d5;1189482-35-6;42461-27-8 (HCl); 54-31-9; 41733-55-5 (sodium); 61422-49-9 (xantinol)

3440

White to light yellow crystalline powder.

1.6±0.1 g/cm3

582.1±60.0 °C at 760 mmHg

220 °C (dec.)(lit.)

305.9±32.9 °C

0.0±1.7 mmHg at 25°C

1.658

3.1

3

7

5

21

481

0

ClC1C([H])=C(C(C(=O)O[H])=C([H])C=1S(N([H])[H])(=O)=O)N([H])C([H])([H])C1=C([H])C([H])=C([H])O1

ZZUFCTLCJUWOSV-UHFFFAOYSA-N

InChI=1S/C12H11ClN2O5S/c13-9-5-10(15-6-7-2-1-3-20-7)8(12(16)17)4-11(9)21(14,18)19/h1-5,15H,6H2,(H,16,17)(H2,14,18,19)

4-chloro-2-(furan-2-ylmethylamino)-5-sulfamoylbenzoic acid

Lasix; Frusemide; Lasix; Furanthril; Furosemid; Errolon; Fusid; Furosemide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~302.35 mM)
H2O : ~0.1 mg/mL (~0.30 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (7.56 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)