用户名： 密   码：
注册 | 忘记密码？
药品详细

Torasemide(托拉塞米)

化学结构式图
中文名
托拉塞米
英文名
Torasemide
分子式
C16H20N4O3S
化学名
1-{4-[(3-methylphenyl)amino]pyridine-3-sulfonyl}-3-(propan-2-yl)urea
分子量
Average: 348.42
Monoisotopic: 348.125611216
CAS号
56211-40-6
ATC分类
C03C 未知;C03C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Torasemide (rINN) or torsemide (USAN) is a pyridine-sulfonylurea type loop diuretic mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. It is marketed under the brand name Demadex. [Wikipedia]

生产厂家
  • Apotex inc etobicoke site
  • Aurobindo pharma ltd
  • Bedford laboratories
  • Hetero drugs ltd
  • Hoffmann la roche inc
  • Luitpold pharmaceuticals inc
  • Meda pharmaceuticals inc
  • Par pharmaceutical inc
  • Pliva pharmaceutical industry inc
  • Roxane laboratories inc
  • Sun pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Dunn CJ, Fitton A, Brogden RN: Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Jan;49(1):121-42. Pubmed
  2. FDA approved new drug bulletin: torsemide (Demadex), trimetrexate glucuronate (neuTrexin). RN. 1994 May;57(5):53-6. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Sulfonylureas
Substructures
  • Sulfonylureas
  • Aliphatic and Aryl Amines
  • Pyridines and Derivatives
  • Sulfonyls
  • Benzene and Derivatives
  • Ureas and Derivatives
  • Aminopyridines and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Sulfonamides
  • Anilines
适应症
药理
Indication For the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Also for the treatment of hypertension alone or in combination with other antihypertensive agents.
Pharmacodynamics Torasemide (INN) or torsemide (USAN) is a novel loop diuretic belonging to pridine sulphonyl urea. It differs form other thiazide diuretics in that a double ring system is incorporated into its structure. Like thiazides, loop diuretics must be secreted into the tubular fluid by proximal tubule cells. In the thick ascending loop Na+ and Cl- reabsorption is accomplished by a Na+/K+/2Cl- symporter. The thick ascending limb has a high reabsorptive capacity and is responsible for reabsorbing 25% of the filtered load of Na+. The loop diuretics act by blocking this symporter. Because of the large absorptive capacity and the amount of Na+ delivered to the ascending limb, loop diuretics have a profound diuretic action. In addition, more distal nephron segments do not have the reabsorptive capacity to compensate for this increased load. The osmotic gradient for water reabsorption is also reduced resulting in an increase in the amount of water excreted.
Mechanism of action Torasemide inhibits the Na+/K+/2Cl--carrier system (via interference of the chloride binding site) in the lumen of the thick ascending portion of the loop of Henle, resulting in a decrease in reabsorption of sodium and chloride. This results in an increase in the rate of delivery of tubular fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma volume contraction increases aldosterone production. The increased delivery and high aldosterone levels promote sodium reabsorption at the distal tubules, and By increasing the delivery of sodium to the distal renal tubule, torasemide indirectly increases potassium excretion via the sodium-potassium exchange mechanism. Torasemide's effects in other segments of the nephron have not been demonstrated. Thus torasemide increases the urinary excretion of sodium, chloride, and water, but it does not significantly alter glomerular filtration rate, renal plasma flow, or acid-base balance. Torasemide's effects as a antihypertensive are due to its diuretic actions. By reducing extracellular and plasma fluid volume, blood pressure is reduced temporarily, and cardiac output also decreases.
Absorption Rapidly absorbed following oral administration. Absolute bioavailability is 80%. Food has no effect on absorption.
Volume of distribution
  • 12 to 15 L [normal adults or in patients with mild to moderate renal failure or congestive heart failure]
Protein binding > 99%
Metabolism
Metabolized via the hepatic CYP2C8 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.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Torasemide
hydroxytorsemide Details
Route of elimination Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance in patients with normal renal function).
Half life 3.5 hours
Clearance Not Available
Toxicity Symptoms of overdose include dehydration, hypovolemia, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, and hemoconcentration. Oral LD50 in rat is 5 g/kg, and intravenous LD50 in rat is 500 mg/kg.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00118 Torsemide Pathway SMP00118
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 164-164 °C Not Available
water solubility Water soluble Not Available
logP 2.3 Not Available
pKa 7.1 Not Available
Predicted Properties
Property Value Source
water solubility 5.96e-02 g/l ALOGPS
logP 1.76 ALOGPS
logP 1.86 ChemAxon
logS -3.8 ALOGPS
pKa (strongest acidic) 5.92 ChemAxon
pKa (strongest basic) 4.2 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 100.19 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 91.89 ChemAxon
polarizability 36.15 ChemAxon
药物相互作用
Drug Interaction
Amifostine Torasemide may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Torasemide should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Amikacin Increased ototoxicity
Capecitabine Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Capecitabine is initiated, discontinued or dose changed.
Cholestyramine Cholestyramine may decrease the bioavailability of Torasemide by inhibiting Torasemide absorption. Monitor for changes in the therapeutic and adverse effects of Torasemide if Cholestyramine is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.
Colesevelam Colesevelam may decrease the bioavailability of Torasemide by inhibiting Torasemide absorption. Monitor for changes in the therapeutic and adverse effects of Torasemide if Colesevelam is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.
Colestipol Colestipol may decrease the bioavailability of Torasemide by inhibiting Torasemide absorption. Monitor for changes in the therapeutic and adverse effects of Torasemide if Colestipol is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.
Delavirdine Delavirdine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Delavirdine is initiated, discontinued or dose changed.
Floxuridine Floxuridine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Floxuridine is initiated, discontinued or dose changed.
Fluconazole Fluconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Fluconazole is initiated, discontinued or dose changed.
Fluorouracil Fluorouracil, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Fluorouracil is initiated, discontinued or dose changed.
Flurbiprofen Flurbiprofen, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Flurbiprofen is initiated, discontinued or dose changed.
Gemfibrozil Gemfibrozil, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Gemfibrozil is initiated, discontinued or dose changed.
Gentamicin Increased ototoxicity
Ibuprofen The NSAID, ibuprofen, may decrease the diuretic and antihypertensive effect of the loop diuretic, torasemide.
Indomethacin The NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, torasemide.
Ketoconazole Ketoconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Ketoconazole is initiated, discontinued or dose changed.
Mefenamic acid Mefanamic acid, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Mefanamic acid is initiated, discontinued or dose changed.
Miconazole Miconazole, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Miconazole is initiated, discontinued or dose changed.
Netilmicin Increased ototoxicity
Nicardipine Nicardipine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Nicardipine is initiated, discontinued or dose changed.
Piroxicam Piroxicam, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Piroxicam is initiated, discontinued or dose changed.
Rituximab Additive antihypertensive effects may occur. Increased risk of hypotension. Consider withholding Torasemide for 12 hours prior to administration of Rituximab.
Sitaxentan Sitaxsentan, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Sitaxsentan is initiated, discontinued or dose changed.
Sulfadiazine Sulfadiazine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Sulfadiazine is initiated, discontinued or dose changed.
Sulfisoxazole Sulfisoxazole, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Sulfisoxazole is initiated, discontinued or dose changed.
Tobramycin Increased ototoxicity
Tolbutamide Tolbutamide, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing its metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Tolbutamide is initiated, discontinued or dose changed.
Trandolapril The loop diuretic, Torasemide, may increase the hypotensive effect of Trandolapril. Torasemide may also increase the nephrotoxicity of Trandolapril.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
食物相互作用
Not Available

返回 | 收藏