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 most bioavailable diuretic orally, even in advanced chronic kidney disease. Its bioavailability is typically above 80% regardless of the patient's condition. Peak serum concentrations have been reported at 1 hour, and co-administration with food does not affect its absorption. Torasemide is primarily metabolized in the liver and excreted in the feces, with approximately 70-80% of the administered dose eliminated via this route. On the other hand, approximately 20-30% of the administered dose is excreted in the urine. The volume of distribution of torasemide is 0.2 L/kg. Kidney disease significantly reduces the clearance of torasemide. Metabolism/Metabolites Torasemide is extensively metabolized in the liver, with only 20% of the dose excreted unchanged in the urine. It is primarily metabolized via hydroxylation, oxidation, and reduction reactions at CYP2C8 and CYP2C9 in the liver, producing five metabolites. The major metabolite, M5, has no pharmacological activity. There are also two minor metabolites, M1, with approximately one-tenth the activity of torasemide, and M3, with activity comparable 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. Known metabolites of torasemide include N-[(4-{[3-(hydroxymethyl)phenyl]imino}-1,4-dihydropyridin-3-yl)sulfonyl]propane-2-carbamoimidinic acid. The mean half-life of torasemide is 3.5 hours.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Due to limited information regarding the use of torasemide during lactation, and the potential for potent diuresis to reduce milk production, alternative medications should be prioritized, especially when breastfeeding newborns or preterm infants. Low-dose torasemide may not suppress lactation.
◉ Effects on Breastfed Infants
No relevant published information was found as of the revision date.
◉ Effects on Lactation and Breast Milk
Potential diuresis, fluid restriction, and chest binding have been used to suppress lactation immediately postpartum. The additional effects of diuretics on other effective lactation suppression measures have not been investigated.
Women with preeclampsia were randomly assigned to receive torasemide 20 mg/day or placebo for 5 days, starting within 24 hours postpartum. 80% of women treated with torasemide breastfed, compared to 75% of women receiving placebo. One mother who received torasemide reported a decrease in breast milk production, while no mother who received a placebo reported a decrease in breast milk production.
Protein Binding
Torasemide has a high binding rate to plasma proteins, exceeding 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 drug formed by the condensation of [(3-methylphenyl)amino]pyridine-3-sulfonic acid with the free amino group of N-isopropylurea. It is a potent loop diuretic used to treat hypertension and edema in patients with congestive heart failure. It is both a loop diuretic and an antihypertensive drug. It is an N-sulfonylurea compound, belonging to the aminopyridine and secondary amino compounds. Its function is similar to 4-aminopyridine. Torasemide is a highly effective loop diuretic. Structurally, it is a pyridinesulfonylurea antihypertensive drug. Torasemide was first approved for clinical use by the U.S. Food and Drug Administration (FDA) in 1993. Torasemide is a loop diuretic. The physiological effect of torasemide is achieved by increasing the diuretic effect of the loop of Henle. Torasemide is an aniline pyridinesulfonylurea drug, belonging to the loop diuretic class. Compared to other loop diuretics, torasemide has a longer duration of action, extensive protein binding in plasma, and a relatively long half-life. Torasemide is a pyridine and sulfonamide derivative that acts as a sodium-potassium-chloride cotransporter inhibitor (loop diuretic). It is used to treat edema associated with congestive heart failure, chronic renal insufficiency, and liver disease. It is also used to treat hypertension. See also: Torasemide sodium (its active ingredient).

---

Drug Indications
Torasemide is indicated for the treatment of edema associated with congestive heart failure, kidney disease, or liver disease. Therefore, torasemide is very effective in cases of renal failure. In addition, torasemide is approved for use alone or in combination with other antihypertensive drugs as an antihypertensive agent.
FDA Label
For the treatment of clinical symptoms associated with congestive heart failure in dogs, including edema and effusion.
For the treatment of clinical symptoms associated with congestive heart failure in dogs, including pulmonary edema. Mechanism of Action As described above, torasemide is a loop diuretic. Its mechanism of action is to reduce oxygen demand in the thick ascending limb of the loop of Henle in the medulla by inhibiting the Na+/K+/Cl- pump on the surface of tubular cell membranes. This effect is achieved by torasemide binding to the chloride ion binding site of transport molecules. Torasemide is known to act on the renin-angiotensin-aldosterone system by inhibiting downstream cascade reactions following angiotensin II activation. This inhibition produces secondary effects, manifested as decreased expression of aldosterone synthase, TGF-β1, and thromboxane A2, as well as reduced aldosterone receptor binding. Pharmacodynamics Torasemide is well known to reduce kidney damage and the severity of acute renal failure. This effect is achieved by increasing urine output, thereby helping to maintain fluid, acid-base, and potassium balance. This effect is achieved by increasing urinary sodium and chloride excretion. Multiple studies have shown that torasemide has a sustained diuretic effect and reduces potassium excretion, which can be explained by its influence on the renin-angiotensin-aldosterone system. This effect is very similar to that of combined furosemide and spironolactone therapy, characterized by decreased plasma brain natriuretic peptide levels and improved left ventricular function indicators. In addition to the above effects, torasemide also has a dual effect: inhibiting aldosterone, thereby exerting a potassium-sparing effect. Studies have shown that torasemide can reduce extracellular fluid volume and blood pressure in hypertensive patients with chronic kidney disease. Furthermore, some reports indicate that torasemide can alleviate myocardial fibrosis by reducing collagen accumulation. This effect is thought to be related to a decrease in aldosterone levels, which has been shown to reduce the production of type I collagen C-terminal protease, an enzyme known to be overexpressed in patients with heart failure.

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.

---

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.

---

View More

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.

---

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