By reversibly binding to the Na+/2Cl-/K+ cotransporter carrier protein, tromesemide reduces or completely eliminates the absorption of NaCl [1].

Absorption, Distribution and Excretion
Torasemide is the diuretic with the highest oral bioavailability even in advanced stages of chronic kidney disease. This bioavailability tends to be higher than 80% regardless of the patient condition. The maximal serum concentration is reported to be of 1 hour and the absorption parameters are not affected by its use concomitantly with food.
Torasemide is mainly hepatically processed and excreted in the feces from which about 70-80% of the administered dose is excreted by this pathway. On the other hand, about 20-30% of the administered dose is found in the urine.
The volume of distribution of torasemide is 0.2 L/kg.
The clearance rate of torasemide is considerably reduced by the presence of renal disorders.

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Metabolism / Metabolites
Torasemide is extensively metabolized in the liver and only 20% of the dose remains unchanged and it is recovered in the urine. Metabolized via the hepatic CYP2C8 and CYP2C9 mainly by reactions of hydroxylation, oxidation and reduction to 5 metabolites. The major metabolite, M5, is pharmacologically inactive. There are 2 minor metabolites, M1, possessing one-tenth the activity of torasemide, and M3, equal in activity to torasemide. Overall, torasemide appears to account for 80% of the total diuretic activity, while metabolites M1 and M3 account for 9% and 11%, respectively.
Torasemide has known human metabolites that include N-[(4-{[3-(hydroxymethyl)phenyl]imino}-1,4-dihydropyridin-3-yl)sulfonyl]propane-2-carbamimidic acid.

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Biological Half-Life
The average half-life of torasemide is 3.5 hours.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Because little information is available on the use of torsemide during breastfeeding and because intense diuresis might decrease lactation, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. Low doses of torsemide may not suppress lactation.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Intense diuresis, fluid restriction and breast binding have been used to suppress lactation immediately postpartum. The added contribution of the diuretic to the other measures, which are effective in suppressing lactation, has not been studied.
Women who delivered following pre-eclampsia were randomized to receive either torsemide 20 mg daily or placebo for 5 days starting within 24 hours after delivery. Eighty percent of the women who received torsemide and 75% of women who received placebo breastfed. One mother who received torsemide and none who received placebo reported a decrease in breastmilk.

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Protein Binding
Torasemide is found to be highly bound to plasma proteins, representing over 99% of the administered dose.

[1]. Ishido, H., et al. Torasemide for the Treatment of Heart Failure. Cardiovascular & Hematological Disorders-Drug Targets. 2008. 8(2), 127–132.
[2]. Goodfriend, T. L., et al. Torsemide inhibits aldosterone secretion in vitro. Life Sciences. 1998. 63(3), PL45–PL50.
[3]. H A Friedel, et al. Torasemide. A review of its pharmacological properties and therapeutic potential. Drugs. 1991 Jan;41(1):81-103.

Torasemide is an N-sulfonylurea obtained by formal condensation of [(3-methylphenyl)amino]pyridine-3-sulfonic acid with the free amino group of N-isopropylurea. It is a potent loop diuretic used for the treatment of hypertension and edema in patients with congestive heart failure. It has a role as a loop diuretic and an antihypertensive agent. It is a N-sulfonylurea, an aminopyridine and a secondary amino compound. It is functionally related to a 4-aminopyridine.
Torasemide is a high-ceiling loop diuretic. Structurally, it is a pyridine-sulfonylurea used as an antihypertensive agent. Torasemide was first approved for clinical use by the FDA in 1993.
Torsemide is a Loop Diuretic. The physiologic effect of torsemide is by means of Increased Diuresis at Loop of Henle.
Torsemide is an anilinopyridine sulfonylurea belonging to the class of loop diuretics. Torsemide has a prolonged duration of action compared to other loop diuretics, is extensively protein bound in plasma and has a relatively long half-life.
A pyridine and sulfonamide derivative that acts as a sodium-potassium chloride symporter inhibitor (loop diuretic). It is used for the treatment of EDEMA associated with CONGESTIVE HEART FAILURE; CHRONIC RENAL INSUFFICIENCY; and LIVER DISEASES. It is also used for the management of HYPERTENSION.
See also: Torasemide sodium (is active moiety of).

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Drug Indication
Torasemide is indicated for the treatment of edema associated with congestive heart failure, renal or hepatic diseases. From this condition, it has been observed that torasemide is very effective in cases of kidney failure. As well, torasemide is approved to be used as an antihypertensive agent either alone or in combination with other antihypertensives.
FDA Label
For treatment of clinical signs, including oedema and effusion, related to congestive heart failure in dogs.
For treatment of clinical signs related to congestive heart failure in dogs, including pulmonary oedema.

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Mechanism of Action
As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface. This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule. Torasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B1 and thromboxane A2 and a reduction on the aldosterone receptor binding.

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Pharmacodynamics
It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control. This effect is obtained by the increase in the excretion of urinary sodium and chloride. Several reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy with [furosemide] and [spironolactone] and it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function. Above the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action. Torasemide has been shown to reduce extracellular fluid volume and blood pressure in hypertensive patients suffering from chronic kidney disease. As well, some reports have indicated that torasemide can reduce myocardial fibrosis by reducing the collagen accumulation. This effect is suggested to be related to the decrease in aldosterone which in order has been shown to reduce the production of the enzyme procollagen type I carboxy-terminal proteinase which is known to be overexpressed in heart failure patients.

C16H20N4O3S

348.4200

348.125

56211-40-6

Torsemide-d7;1189375-06-1

41781

White to off-white solid powder

1.3±0.1 g/cm3

163-164ºC

1.595

3.53

3

5

5

24

518

0

S(C1C([H])=NC([H])=C([H])C=1N([H])C1=C([H])C([H])=C([H])C(C([H])([H])[H])=C1[H])(N([H])C(N([H])C([H])(C([H])([H])[H])C([H])([H])[H])=O)(=O)=O

NGBFQHCMQULJNZ-UHFFFAOYSA-N

InChI=1S/C16H20N4O3S/c1-11(2)18-16(21)20-24(22,23)15-10-17-8-7-14(15)19-13-6-4-5-12(3)9-13/h4-11H,1-3H3,(H,17,19)(H2,18,20,21)

1-[4-(3-methylanilino)pyridin-3-yl]sulfonyl-3-propan-2-ylurea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~25 mg/mL (~71.75 mM)

Solubility in Formulation 1: ≥ 1 mg/mL (2.87 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 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1 mg/mL (2.87 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 10.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 1 mg/mL (2.87 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 10.0 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.)