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药品详细

Aliskiren(阿利吉仑)

化学结构式图
中文名
阿利吉仑
英文名
Aliskiren
分子式
C30H53N3O6
化学名
(2S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2,2-dimethylethyl)-4-hydroxy-7-{[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl}-8-methyl-2-(propan-2-yl)nonanamide
分子量
Average: 551.7583
Monoisotopic: 551.393436443
CAS号
173334-57-1
ATC分类
C09X 未知
药物类型
small molecule
阶段
approved
商品名
同义名
基本介绍

Aliskiren is a renin inhibitor. It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension.

生产厂家
  • Novartis pharmaceuticals corp
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP: Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005 Mar 1;111(8):1012-8. Epub 2005 Feb 21. Pubmed
  2. Staessen JA, Li Y, Richart T: Oral renin inhibitors. Lancet. 2006 Oct 21;368(9545):1449-56. Pubmed
  3. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP: Clinical pharmacokinetics and pharmacodynamics of aliskiren. Clin Pharmacokinet. 2008;47(8):515-31. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Carbonyl Compounds
  • Phenols and Derivatives
  • Ethers
  • Catechols
  • Anisoles
  • Phenyl Esters
Substructures
  • Carbonyl Compounds
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Carbamates and Derivatives
  • Amino Alcohols
  • Catechols
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
适应症
药理
Indication For the treatment of mild to moderate hypertension. It may be used alone or in combination with other antihypertensive agents.
Pharmacodynamics Aliskiren is a nonpeptide renin inhibitor marketed under the trade name Tekturna by Novartis.
Mechanism of action Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits renin release, thus providing a negative feedback to the system. This cycle, from renin through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known. All agents that inhibit the RAAS, including renin inhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma renin concentration. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of PRA. During treatment with aliskiren, however, the effect of increased renin levels is blocked, so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents. PRA reductions in clinical trials ranged from approximately 50%-80%, were not dose-related and did not correlate with blood pressure reductions. The clinical implications of the differences in effect on PRA are not known.
Absorption Rapidly absorbed following oral administration. Absolute bioavailability = 2.6%
Volume of distribution Not Available
Protein binding 47-51%
Metabolism
Approximately 80% of the drug in plasma following oral administration is unchanged. Cytochrome P450 (CYP) 3A4 oxidation produces two major metabolites that account for approximately 5% of the drug in plasma. Aliskiren is eliminated primarily through the biliary/fecal route as unchanged drug and, to a lesser extent, via oxidative metabolism via CYP3A4. Only 0.6% of the oral dose is recovered in urine.
Route of elimination About one fourth of the absorbed dose appears in the urine as parent drug.
Half life 24-41 hours
Clearance Not Available
Toxicity The most likely manifestation of overdosage would be hypotension.
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Experimental Properties
Property Value Source
water solubility Highly soluble in water (as hemifumarate salt) Not Available
logP 3.3 Not Available
Predicted Properties
Property Value Source
water solubility 2.10e-03 g/l ALOGPS
logP 3.87 ALOGPS
logP 3.12 ChemAxon
logS -5.4 ALOGPS
pKa (strongest acidic) 14.56 ChemAxon
pKa (strongest basic) 9.57 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 146.13 ChemAxon
rotatable bond count 19 ChemAxon
refractivity 154.32 ChemAxon
polarizability 64.25 ChemAxon
药物相互作用
Drug Interaction
Azilsartan medoxomil Azilsartan medoxomil used in combination with aliskiren may lead to hyperkalemia, hypotension, and nephrotoxicity.
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
食物相互作用
Not Available

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