药品详细
Enalapril (依那普利 )
化学结构式图
中文名
依那普利
英文名
Enalapril
分子式
Not Available
化学名
(2S)-1-[(2S)-2-{[(2R)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid
分子量
Average: 376.4467
Monoisotopic: 376.199822016
Monoisotopic: 376.199822016
CAS号
75847-73-3
ATC分类
C09A 未知
药物类型
small molecule
阶段
商品名
Bonuten;Gadopril (Gador (Argentina));Kinfil (Nova Argentia (Argentina));Vasotec (Merck Frosst (Canada));Vasotec IV (Sandoz (Canada));
同义名
Enalapril Maleate;Enalaprila [INN-Spanish];Enalaprilat;Enalaprilum [INN-Latin];
基本介绍
Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to enalaprilat following oral administration. Enalaprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Enalapril may be used to treat essential or renovascular hypertension and symptomatic congestive heart failure.
生产厂家
- Apotex inc
- Apothecon inc div bristol myers squibb
- Bedford laboratories div ben venue laboratories inc
- Biovail laboratories international srl
- Hikma farmaceutica (portugal) sa
- Hospira inc
- Ivax pharmaceuticals inc sub teva pharmaceuticals usa
- Krka dd novo mesto
- Lek pharmaceuticals d d
- Mylan pharmaceuticals inc
- Ranbaxy laboratories ltd
- Sandoz inc
- Taro pharmaceutical industries ltd
- Teva parenteral medicines inc
- Teva pharmaceuticals usa inc
- Watson laboratories inc
- Wockhardt americas inc
封装厂家
参考
| Synthesis Reference | Not Available |
| General Reference | Not Available |
剂型
| Form | Route | Strength |
|---|---|---|
| Injection, solution | Intravenous | 1.25 mg/ml |
| Tablet | Oral | 10 mg |
| Tablet | Oral | 2.5 mg |
| Tablet | Oral | 20 mg |
| Tablet | Oral | 5 mg |
规格
| Unit description | Cost | Unit |
|---|---|---|
| Enalapril maleate powder | 9.18 USD | g |
| Enalaprilat 1.25 mg/ml vial | 3.6 USD | ml |
| Vasotec 20 mg tablet | 3.36 USD | tablet |
| Vaseretic 10-25 mg tablet | 3.15 USD | tablet |
| Vasotec 10 mg tablet | 2.63 USD | tablet |
| Vasotec 5 mg tablet | 2.08 USD | tablet |
| Vasotec 2.5 mg tablet | 1.65 USD | tablet |
| Enalapril maleate 20 mg tablet | 1.56 USD | tablet |
| Vaseretic 5-12.5 mg tablet | 1.49 USD | tablet |
| Vasotec 20 mg Tablet | 1.34 USD | tablet |
| Vasotec 10 mg Tablet | 1.11 USD | tablet |
| Enalapril maleate 10 mg tablet | 1.09 USD | tablet |
| Enalapril maleate 5 mg tablet | 1.03 USD | tablet |
| Vasotec 5 mg Tablet | 0.92 USD | tablet |
| Enalapril maleate 2.5 mg tablet | 0.82 USD | tablet |
| Vasotec 2.5 mg Tablet | 0.78 USD | tablet |
| Apo-Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Co Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Mylan-Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Novo-Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Pms-Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Ratio-Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Sandoz Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Taro-Enalapril 20 mg Tablet | 0.75 USD | tablet |
| Apo-Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Co Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Mylan-Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Novo-Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Pms-Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Ratio-Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Sandoz Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Taro-Enalapril 10 mg Tablet | 0.62 USD | tablet |
| Apo-Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Co Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Mylan-Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Novo-Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Pms-Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Ratio-Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Sandoz Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Taro-Enalapril 5 mg Tablet | 0.52 USD | tablet |
| Apo-Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Co Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Mylan-Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Novo-Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Pms-Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Ratio-Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Sandoz Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
| Taro-Enalapril 2.5 mg Tablet | 0.44 USD | tablet |
化合物类型
| Type | small molecule |
| Classes |
|
| Substructures |
|
适应症
ANTIHYPERTENSIVES 降血压;
药理
| Indication | For the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics. | ||||||
| Pharmacodynamics | Enalapril is a prodrug that is rapidly metabolized by liver esterases to enalaprilat following oral administration. Enalapril itself has little pharmacologic activity. Enalaprilat lowers blood pressure by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of enalaprilat by causing increased vasodilation and decreased blood pressure. | ||||||
| Mechanism of action | There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Enalaprilat, the principle active metabolite of enalapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Enalapril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Enalaprilat's affinity for ACE is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that enalapril. | ||||||
| Absorption | 55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity. | ||||||
| Volume of distribution | Not Available | ||||||
| Protein binding | 50-60% of enalaprilat is bound to plasma proteins | ||||||
| Metabolism |
~ 60% of absorbed dose is extensively hydrolyzed to enalaprilat, primarily by liver esterases |
||||||
| Route of elimination | Excretion of enalapril is primarily renal. | ||||||
| Half life | < 2 hours for unchanged enalapril in health individuals, may be increased in those with congestive heart failure (3.4 and 5.8 hours for single 5- and 10-mg doses, respectively). The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours. | ||||||
| Clearance | Not Available | ||||||
| Toxicity | Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue. | ||||||
| Affected organisms |
|
||||||
| Pathways |
|
理化性质
| Properties | |||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| State | solid | ||||||||||||||||||||||||||||||||||||
| Melting point | 143-144.5oC | ||||||||||||||||||||||||||||||||||||
| Experimental Properties |
|
||||||||||||||||||||||||||||||||||||
| Predicted Properties |
|
||||||||||||||||||||||||||||||||||||
药物相互作用
| Drug | Interaction |
|---|---|
| Amiloride | Increased risk of hyperkalemia |
| Drospirenone | Increased risk of hyperkalemia |
| Lithium | The ACE inhibitor increases serum levels of lithium |
| Potassium | Increased risk of hyperkalemia |
| Rifampin | Rifampin, a strong CYP3A4 inducer, may increase the metabolism of enalapril. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of enalapril if rifampin is initiated, discontinued or dose changed. |
| Spironolactone | Increased risk of hyperkalemia |
| Tizanidine | Tizanidine increases the risk of hypotension with the ACE inhibitor |
| Tobramycin | Increased risk of nephrotoxicity |
| Treprostinil | Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. |
| Triamterene | Increased risk of hyperkalemia |
食物相互作用
- Enalapril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.
- Herbs that may attenuate the antihypertensive effect of enalapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
- High salt intake may attenuate the antihypertensive effect of enalapril.
- Take without regard to meals.
收藏