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药品详细

Telmisartan(替米沙坦)

化学结构式图
中文名
替米沙坦
英文名
Telmisartan
分子式
C33H30N4O2
化学名
2-(4-{[4-methyl-6-(1-methyl-1H-1,3-benzodiazol-2-yl)-2-propyl-1H-1,3-benzodiazol-1-yl]methyl}phenyl)benzoic acid
分子量
Average: 514.6169
Monoisotopic: 514.236876224
CAS号
144701-48-4
ATC分类
C09C 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Telmisartan is an angiotensin II receptor antagonist (ARB) used in the management of hypertension. Generally, angiotensin II receptor blockers (ARBs) such as telmisartan bind to the angiotensin II type 1 (AT1) receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. Recent studies suggest that telmisartan may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects.

生产厂家
  • Boehringer ingelheim
封装厂家
参考
Synthesis Reference
  1. Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. Pubmed
General Reference
  1. Sharpe M, Jarvis B, Goa KL: Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501-29. Pubmed
  2. Smith DH: Treatment of hypertension with an angiotensin II-receptor antagonist compared with an angiotensin-converting enzyme inhibitor: a review of clinical studies of telmisartan and enalapril. Clin Ther. 2002 Oct;24(10):1484-501. Pubmed
  3. Kumar AS, Ghosh S, Mehta GN: Efficient and improved synthesis of Telmisartan. Beilstein J Org Chem. 2010 Mar 11;6:25. Pubmed
  4. Galzerano D, Capogrosso C, Di Michele S, Galzerano A, Paparello P, Lama D, Gaudio C: New standards in hypertension and cardiovascular risk management: focus on telmisartan. Vasc Health Risk Manag. 2010 Mar 24;6:113-33. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Biphenyl and Derivatives
  • Cinnamates
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Benzimidazoles
  • Carboxylic Acids and Derivatives
  • Phenylpropenes
  • Benzene and Derivatives
  • Biphenyl and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Cinnamaldehydes
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
  • Cinnamates
适应症
药理
Indication Used alone or in combination with other classes of antihypertensives for the treatment of hypertension. Also used in the treatment of diabetic nephropathy in hypertensive patients with type 2 diabetes mellitus, as well as the treatment of congestive heart failure (only in patients who cannot tolerate ACE inhibitors).
Pharmacodynamics Telmisartan is an orally active nonpeptide angiotensin II antagonist that acts on the AT1 receptor subtype. It has the highest affinity for the AT1 receptor among commercially available ARBS and has minimal affinity for the AT2 receptor. New studies suggest that telmisartan may also have PPARγ agonistic properties that could potentially confer beneficial metabolic effects, as PPARγ is a nuclear receptor that regulates specific gene transcription, and whose target genes are involved in the regulation of glucose and lipid metabolism, as well as anti-inflammatory responses. This observation is currently being explored in clinical trials. Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Telmisartan works by blocking the vasoconstrictor and aldosterone secretory effects of angiotensin II.
Mechanism of action Telmisartan interferes with the binding of angiotensin II to the angiotensin II AT1-receptor by binding reversibly and selectively to the receptors in vascular smooth muscle and the adrenal gland. As angiotensin II is a vasoconstrictor, which also stimulates the synthesis and release of aldosterone, blockage of its effects results in decreases in systemic vascular resistance. Telmisartan does not inhibit the angiotensin converting enzyme, other hormone receptors, or ion channels. Studies also suggest that telmisartan is a partial agonist of PPARγ, which is an established target for antidiabetic drugs. This suggests that telmisartan can improve carbohydrate and lipid metabolism, as well as control insulin resistance without causing the side effects that are associated with full PPARγ activators.
Absorption Absolute bioavailability depends on dosage. Food slightly decreases the bioavailability (a decrease of about 6% is seen when the 40-mg dose is administered with food).
Volume of distribution
  • 500 L
Protein binding Highly bound to plasma proteins (>99.5%), mainly albumin and a1-acid glycoprotein. Binding is not dose-dependent.
Metabolism
Minimally metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Route of elimination Following either intravenous or oral administration of 14C-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively).
Half life Bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours.
Clearance
  • >800 mL/min
Toxicity Intravenous LD50 in rats is 150-200 mg/kg in males and 200 to 250 mg/kg in females. Acute oral toxicity is low: no deaths and no changes occurred in rats or dogs at 2000 mg/kg, the highest dose tested. Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 261-263 °C Not Available
water solubility Practically insoluble Not Available
logP 7.7 Not Available
Caco2 permeability -4.82 ADME Research, USCD
Predicted Properties
Property Value Source
water solubility 3.50e-03 g/l ALOGPS
logP 6.66 ALOGPS
logP 6.04 ChemAxon
logS -5.2 ALOGPS
pKa (strongest acidic) 3.65 ChemAxon
pKa (strongest basic) 6.13 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 72.94 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 164.49 ChemAxon
polarizability 58.61 ChemAxon
药物相互作用
Drug Interaction
Acetylsalicylic acid Concomitant use of Telmisartan and Acetylsalicylic acid may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Amifostine Telmisartan may increase the hypotensive effect of Amifostine. At chemotherapeutic doses of Amifostine, Telmisartan should be withheld for 24 hours prior to Amifostine administration. Use caution at lower doses of Amifostine.
Amiloride Telmisartan may increase the hyperkalemic effect of Amiloride. Monitor for increased serum potassium concentrations during concomitant therapy.
Celecoxib Concomitant use of Telmisartan and Celecoxib may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Diclofenac Concomitant use of Telmisartan and Diclofenac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Diflunisal Concomitant use of Telmisartan and Diflunisal may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Digoxin Telmisartan may increase plasma Digoxin concentrations. Monitor Digoxin levels and adjust dose as required if Telmisartan is initiated, discontinued or dose changed.
Drospirenone Telmisartan may increase the hyperkalemic effect of Drospirenone. Monitor for increased serum potassium concentrations during concomitant therapy.
Fenoprofen Concomitant use of Telmisartan and Fenoprofen may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Flurbiprofen Concomitant use of Telmisartan and Flurbiprofen may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Indomethacin Concomitant use of Telmisartan and Indomethacin may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Ketoprofen Concomitant use of Telmisartan and Ketoprofen may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Ketorolac Concomitant use of Telmisartan and Ketorolac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Lithium Telmisartan may increase serum Lithium concentrations. Monitor serum Lithium levels during concomitant therapy to avoid Lithium toxicity.
Lumiracoxib Concomitant use of Telmisartan and Lumiracoxib may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Meclofenamic acid Concomitant use of Telmisartan and Meclofenamic acid may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Meloxicam Concomitant use of Telmisartan and Meloxicam may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Nabumetone Concomitant use of Telmisartan and Nabumetone may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Naproxen Concomitant use of Telmisartan and Naproxen may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Oxaprozin Concomitant use of Telmisartan and Oxaprozin may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Piroxicam Concomitant use of Telmisartan and Piroxicam may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Potassium Potassium may increase the hyperkalemic effect of Telmisartan. Monitor serum potassium levels during concomitant use.
Potassium Chloride Potassium Chloride may increase the hyperkalemic effect of Telmisartan. Monitor serum potassium levels during concomitant use.
Rituximab Telmisartan may increase the hypotensive effect of Rituximab. Telmisartan should be withheld prior to and throughout Rituximab administration.
Spironolactone Telmisartan may increase the hyperkalemic effect of Spironolactone. Monitor for increased serum potassium concentrations during concomitant therapy.
Sulindac Concomitant use of Telmisartan and Sulindac may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Tiaprofenic acid Concomitant use of Telmisartan and Tiaprofenic acid may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Tobramycin Increased risk of nephrotoxicity
Tolmetin Concomitant use of Telmisartan and Tolmetin may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.
Trandolapril The angiotensin II receptor blocker, Telmisartan, may increase the adverse effects of Trandolapril.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triamterene Telmisartan may increase the hyperkalemic effect of Triamterene. Monitor for increased serum potassium concentrations during concomitant therapy.
食物相互作用
Not Available

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