Enalapril

Identification

Summary

Enalapril is a prodrug of an ACE inhibitor used to treat hypertension and congestive heart failure.

Brand Names

Epaned, Vaseretic, Vasotec

Generic Name

Enalapril

DrugBank Accession Number

DB00584

Background

Enalapril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor drug class that works on the renin-angiotensin-aldosterone system, which is responsible for the regulation of blood pressure and fluid and electrolyte homeostasis. Enalapril is an orally-active and long-acting nonsulphydryl antihypertensive agent that suppresses the renin-angiotensin-aldosterone system to lower blood pressure. It was developed from a targeted research programmed using molecular modelling.² Being a prodrug, enalapril is rapidly biotransformed into its active metabolite, enalaprilat, which is responsible for the pharmacological actions of enalapril. The active metabolite of enalapril competitively inhibits the ACE to hinder the production of angiotensin II, a key component of the renin-angiotensin-aldosterone system that promotes vasoconstriction and renal reabsorption of sodium ions in the kidneys. Ultimately, enalaprilat works to reduce blood pressure and blood fluid volume.

Commonly marketed under the trade name Vasotec, enalapril was first approved by the FDA in 1985 for the management of hypertension, heart failure, and asymptomatic left ventricular dysfunction. It is also found in a combination product containing hydrochlorothiazide that is used for the management of hypertension. The active metabolite enalaprilat is also available in oral tablets and intravenous formulations for injection.

Type

Small Molecule

Groups

Approved, Vet approved

Structure

3D

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Similar Structures

Structure for Enalapril (DB00584)

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Weight

Average: 376.4467
Monoisotopic: 376.199822016

Chemical Formula

C₂₀H₂₈N₂O₅

Synonyms

• (S)-1-(N-(1-(ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline
• (S)-1-{(S)-2-[1-((S)-Ethoxycarbonyl)-3-phenyl-propylamino]-propionyl}-pyrrolidine-2-carboxylic acid
• 1-(N-((S)-1-carboxy-3-phenylpropyl)-L-alanyl)-L-proline 1'-ethyl ester
• ánalapril
• Enalapril
• Enalaprila
• Enalaprilum

External IDs

• L 154739-01 D
• MK 421

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Pharmacology

Indication

Indicated for the management of essential or renovascular hypertension ¹⁰ as monotherapy or in combination with other antihypertensive agents, such as thiazide diuretics, for an additive effect.^Label

Indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis.^Label

Indicated for the management of asymptomatic left ventricular dysfunction in patients with an ejection fraction of ≤ to 35 percent to decrease the rate of development of overt heart failure and the incidence of hospitalization for heart failure.^Label

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Management of	Diabetic nephropathy		••• •••••
Used in combination to manage	High blood pressure (hypertension)	Combination Product in combination with: Nitrendipine (DB01054)	••••••••••••	•••••	••••• •••••••• •••••••••••• •••••••••• •••• •••••••••••	••••••
Used in combination to manage	Hypertension	Combination Product in combination with: Hydrochlorothiazide (DB00999)	••••••••••••
Treatment of	Hypertension		••• •••••	•••••••••
Management of	Hypertension		••••••••••••

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Contraindications & Blackbox Warnings

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Pharmacodynamics

Enalapril is an antihypertensive agent that exhibits natriuretic and uricosuric properties. Enalapril lowers blood pressure in all grades of essential and renovascular hypertension, and peripheral vascular resistance without causing an increase in heart rate.⁶ Individuals with low-renin hypertensive population were still responsive to enalapril.^Label The duration of hypertensive effect in the systolic and diastolic blood pressure persists for at least 24 hours following initial administration of a single oral dose, and repeated daily administration of enalapril confers an additional reduction in blood pressure and a steady-state antihypertensive response may take several weeks.⁷ In patients with severe congestive heart failure and inadequate clinical response to conventional antihypertensive therapies, treatment with enalapril resulted in improvements in cardiac performance as observed by a reduction in both preload and afterload, and improved clinical status long-term.⁶ Furthermore, enalapril was shown to increase cardiac output and stroke volume while decreasing pulmonary capillary wedge pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. In clinical studies, enalapril reduced left ventricular mass, and did not affect cardiac function or myocardial perfusion during exercise.⁵ Enalapril is not highly associated with the risk of bradycardia unlike most diuretics and beta-blockers ⁶ and it does not produce rebound hypertension upon discontinuation of therapy.⁵

Enalapril is not reported to produce hypokalaemia, hyperglycaemia, hyperuricaemia or hypercholesterolaemia. In the kidneys, enalapril was shown to increase renal blood flow and decrease renal vascular resistance. It also augmented the glomerular filtration rate in patients with a glomerular filtration rate less than 80 mL/min.⁵ When used in combination, enalapril was shown to attenuate the extent of drug-induced hypokalemia caused by hydrochlorothiazide ⁶ and the antihypertensive effects of both drugs were potentiated.²

Mechanism of action

The renin-angiotensin-aldosterone system (RAAS) is a signaling pathway that works in synergism with the sympathetic system to regulate blood pressure and fluid and electrolyte homeostasis. Activation of this system upon stimulation by different factors, such as low blood pressure and nerve impulses, leads to increased release of norepinephrine (NE) from sympathetic nerve terminals and effects on the vascular growth, vasoconstriction, and salt retention in the kidneys.⁹ Renin is released from Renin acts on the precursor prottein angiotensinogen, which is a plasma globulin synthesized from the liver, to produce cleaved peptide hormone angiotensin I.⁹ Angiotensin I then can be further cleaved by ACE to produce angiotensin II, a vasoconstrictive peptide hormone.^Label Present in different isoforms, angiotensin converting enzyme (ACE) is peptidyl dipeptidase enzyme expressed in various tissues, including the vascular tissues, such as the heart, brain, and kidneys.⁹ ACE also plays a role in inactivation of bradykinin, a potent vasodepressor peptide.^9,Label Angiotensin II mediates various actions on the body by working on its G-protein coupled receptors, AT1 and AT2.⁹ It causes direct vasoconstriction of precapillary arterioles and postcapillary venules, inhibits the reuptake of NE thereby increasing available levels, stimulates the release of catecholamines from the adrenal medulla, reduces urinary excretion of sodium ions and water by promoting proximal tubular reabsorption, stimulates synthesis and release of aldosterone from the adrenal cortex, and stimulates hypertrophy of both vascular smooth muscle cells and cardiac myocytes.¹¹

Enalapril is a pharmacologically inactive prodrug that requires hepatic biotransformation to form enalaprilat, its active metabolite that works on the RAAS to inhibit ACE.^Label Biotransformation is critial for the therapeutic actions of the drug, as enalapril itself is only a weak inhibitor of ACE.⁴ ACE inhibition results in reduced production and plasma levels of angiotensin II, increased plasma renin activity due to the loss of feedback inhibition by angiotensin II, and decreased aldosterone secretion.¹⁰ However, plasma aldosterone levels usually return to normal during long-term administration of enalapril.⁷ Decreased levels of angiotensin II subsequently leads to the dilatation of peripheral vessles and reduced vascular resistance which in turn lower blood pressure.⁷ While inhibition of ACE leading to suppression of RAAS is thought to be the primary mechanism of action of enalapril, the drug was shown to still exert antihypertensive effects on individuals with low-renin hypertension. It is suggested that enalapril may mediate its pharmacological actions via other modes of action that are not fully understood.^Label As ACE is structurally similar to kininase I, which is a carboxypeptidase that degrades bradykinin, whether increased levels of bradykinin play a role in the therapeutic effects of enalapril remains to be elucidated.^Label

Target	Actions	Organism
AAngiotensin-converting enzyme	inhibitor	Humans

Absorption

Following oral administration, the peak plasma concentrations (Cmax) of enalapril is achieved within 1 hour post dosing while the Cmax of enalaprilat occurs at three to four hours post dosing.^Label The steady-state is achieved by the fourth daily dose and there is no accumulation with repeated dosing.⁵ However, accumulation of enalaprilat may occur in patients with creatinine clearance less than 30 mL/min.⁴ Food intake is reported to have a minimal effect on drug absorption.¹ Following oral administration, about 60% of enalapril was absorbed.^Label Bioavailability of enalapril averaged about 40% when intravenous enalaprilat was used as a reference standard.²

Volume of distribution

The volume of distribution of enalapril has not been established. Enalaprilat is shown to penetrate into most tissuesm, in particular the kidneys and vascular tissuem, although penetration of the blood-brain barrier has not been demonstrated after administration at therapeutic doses.⁷ In dog studies, enalapril and enalaprilat cross the blood-brain barrier poorly.¹⁰ Minimal penetration occurs into breast milk but significant fetal transfer occurs.⁷ The drug crosses the placental barrier in rats and hamsters.¹⁰

Protein binding

It is reported that less than 50% of enalaprilat is bound to human plasma proteins, based on limited data from binding studies of enalaprilat in human plasma both by equilibrium dialysis and by ultrafiltration.^2,7

Metabolism

About 60% of the absorbed dose is extensively hydrolyzed to enalaprilat via de-esterification mediated by hepatic esterases.^Label In humans, metabolism beyond bioactivation to enalaprilat is not observed.⁵

Hover over products below to view reaction partners

• Enalapril
  • Enalaprilat

Route of elimination

Enalapril is mainly eliminated through renal excretion, where approximately 94% of the total dose is excreted via urine or feces as either enalaprilat or unchanged parent compound.^Label About 61% and 33% of the total dose can be recovered in the urine and feces, respectively.⁷ In the urine, about 40% of the recovered dose is in the form of enalaprilat.^Label

Half-life

The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours. The prolonged terminal half-life is due to the binding of enalaprilat to ACE.⁵

Clearance

Following oral administration in healthy male volunteers, the renal clearance was approximately 158 ± 47 mL/min.⁸ It is reported that enalapril and enalaprilat are undetectable in the plasma by 4 hours post-dosing.³

Adverse Effects

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Toxicity

LD₅₀ and Overdose

Oral LD₅₀ in rats is 2973 mg/kg.^MSDS Lethality was observed with single oral doses of enalapril above 1000 mg/kg in mice and greater than or equal to 1775 mg/kg in rats. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril, respectively.¹⁰ While there is limited data about enalapril overdose in humans, overdosage may result in marked hypotension and stupor based on the pharmacological properties of the drug. Most common adverse effects of enalapril include cough, hypotension, stupor, headache, dizziness and fatigue. If hypotension is seen, usual treatment of intravenous infusion of normal saline solution is recommended. Enalaprilat may be removed from systemic circulation with the use of hemodialysis. It has been removed from neonatal circulation by peritoneal dialysis.^Label

Nonclinical toxicology

Maternal and fetal toxicity occudred in some rabbits treated with enalapril at doses of 1 mg/kg/day or more. There was no fetotoxicity, expressed as a decrease in average fetal weight, or teratogenicity in rats treated with enalapril at doses up to 200 mg/kg/day, which is about 333 times the maximum human dose.¹⁰ In mice and rats receiving enalapril at doses ranging from 90 to 180 mg/kg/day, there was no evidence of a tumorigenic effect. Neither enalapril or its active metabolite were shown to be mutagenic or genotoxic in in vitro and in vivo studies. There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril. ^Label

Use in special populations

Caution is warranted in patients who are concurrently using another ACE inhibitors with enalapril, as there have been incidences of agranulocytosis with the use of captopril, which is another ACE inhibitor. This adverse event may be particularly significant in patients with renal impairment or collagen vascular disease.^Label As enalapril and enalaprilat were shown to be secreted in human milk in trace amounts, the use of enalaprilat in nursing women is not recommended.¹⁰ Significant fetal transfer occurs with enalapril and enalaprilat thus the use of the drug in pregnant women should be strongly avoided. Caution is advised when enalapril is used in patients who are elderly or with renal impairment, as dosage adjustments may be appropriate. The antihypertensive effect of angiotensin converting enzyme inhibitors is generally lower in individuals of African descent, usually a low-renin hypertensive population.^Label

Pathways

Pathway	Category
Enalapril Metabolism Pathway	Drug metabolism
Enalapril Action Pathway	Drug action

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Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abaloparatide	The risk or severity of adverse effects can be increased when Enalapril is combined with Abaloparatide.
Acamprosate	The excretion of Acamprosate can be decreased when combined with Enalapril.
Acebutolol	Enalapril may increase the hypotensive activities of Acebutolol.
Aceclofenac	The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Enalapril.
Acemetacin	The risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Enalapril.

Food Interactions

• Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice). Additive hypertensive effects may occur.
• Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
• Take with or without food. The absorption is unaffected by food.

Products

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Enalapril maleate	9O25354EPJ	76095-16-4	OYFJQPXVCSSHAI-QFPUQLAESA-N
Enalapril sodium	94A7UFL2SI	149404-21-7	FTTHROYWFRGKST-BDURURIASA-M

Active Moieties

Name	Kind	UNII	CAS	InChI Key
Enalaprilat	prodrug	Q508Q118JM	76420-72-9	LZFZMUMEGBBDTC-QEJZJMRPSA-N

Product Images

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International/Other Brands

Acetec (Alphapharm) / Acetensil (Grünenthal) / Alapren (Ranbaxy) / Amotac (Mass Pharma) / Amprace (Merck Sharp & Dohme) / Dilvas (Cipla) / Diotensil (Mintlab) / Drepatil (Fada) / Enace (Abbott) / EnaHexal (Sandoz) / Enal (East West) / Enalapoten (Del Bel) / Enpril (Wockhardt) / Feliberal (Silanes) / Gadopril (Gador (Argentina)) / Glioten (Bago) / Kinfil (Nova Argentia (Argentina)) / Vasotec IV (Sandoz (Canada))

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Act Enalapril	Tablet	8 mg	Oral	TEVA Canada Limited	2007-10-17	Not applicable
Act Enalapril	Tablet	4 mg	Oral	TEVA Canada Limited	2007-10-17	Not applicable
Act Enalapril	Tablet	16 mg	Oral	TEVA Canada Limited	2007-10-17	Not applicable
Act Enalapril	Tablet	2 mg	Oral	TEVA Canada Limited	2007-10-17	Not applicable
Enalapril	Tablet	8 mg	Oral	Sivem Pharmaceuticals Ulc	2015-08-10	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Apo-enalapril	Tablet	5 mg	Oral	Apotex Corporation	1993-12-31	Not applicable
Apo-enalapril	Tablet	20 mg	Oral	Apotex Corporation	1993-12-31	Not applicable
Apo-enalapril	Tablet	2.5 mg	Oral	Apotex Corporation	1993-12-31	Not applicable
Apo-enalapril	Tablet	10 mg	Oral	Apotex Corporation	1993-12-31	Not applicable
Ava-enalapril	Tablet	5.0 mg	Oral	Avanstra Inc	2011-10-11	2014-08-21

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
ACESISTEM	Enalapril (20 MG) + Hydrochlorothiazide (12.5 MG)	Tablet	Oral	Alfasigma s.p.a.	2014-07-08	Not applicable
ACESISTEM	Enalapril (20 MG) + Hydrochlorothiazide (12.5 MG)	Tablet	Oral	Alfasigma s.p.a.	2014-07-08	2022-04-14
ACESISTEM	Enalapril (20 MG) + Hydrochlorothiazide (12.5 MG)	Tablet	Oral	Alfasigma s.p.a.	2014-07-08	Not applicable
ATOVER	Enalapril maleate (10 MG) + Lercanidipine hydrochloride (10 MG)	Tablet, coated	Oral	Recordati Industria Chimica E Farmaceutica S.P.A.	2014-07-08	Not applicable
ATOVER	Enalapril maleate (20 MG) + Lercanidipine hydrochloride (10 MG)	Tablet, coated	Oral	Recordati Industria Chimica E Farmaceutica S.P.A.	2014-07-08	Not applicable

Categories

ATC Codes

C09BA02 — Enalapril and diuretics

• C09BA — ACE inhibitors and diuretics
• C09B — ACE INHIBITORS, COMBINATIONS
• C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• C — CARDIOVASCULAR SYSTEM

C09BB06 — Enalapril and nitrendipine

• C09BB — ACE inhibitors and calcium channel blockers
• C09B — ACE INHIBITORS, COMBINATIONS
• C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• C — CARDIOVASCULAR SYSTEM

C09BB02 — Enalapril and lercanidipine

• C09BB — ACE inhibitors and calcium channel blockers
• C09B — ACE INHIBITORS, COMBINATIONS
• C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• C — CARDIOVASCULAR SYSTEM

C09AA02 — Enalapril

• C09AA — ACE inhibitors, plain
• C09A — ACE INHIBITORS, PLAIN
• C09 — AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• C — CARDIOVASCULAR SYSTEM

Drug Categories

• ACE Inhibitors and Calcium Channel Blockers
• ACE Inhibitors and Diuretics
• Agents Acting on the Renin-Angiotensin System
• Agents causing angioedema
• Agents causing hyperkalemia
• Agents Causing Muscle Toxicity
• Amino Acids, Peptides, and Proteins
• Angiotensin-Converting Enzyme Inhibitors
• Antihypertensive Agents
• Antihypertensive Agents Indicated for Hypertension
• Cardiovascular Agents
• Decreased Blood Pressure
• Dipeptides
• Drugs causing inadvertant photosensitivity
• Enzyme Inhibitors
• Hypotensive Agents
• OAT1/SLC22A6 inhibitors
• OAT3/SLC22A8 Inhibitors
• OATP1B1/SLCO1B1 Substrates
• Oligopeptides
• P-glycoprotein inhibitors
• Peptides
• Photosensitizing Agents
• Protease Inhibitors

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.

Kingdom

Organic compounds

Super Class

Organic acids and derivatives

Class

Carboxylic acids and derivatives

Sub Class

Amino acids, peptides, and analogues

Direct Parent

Dipeptides

Alternative Parents

Proline and derivatives / Alpha amino acid esters / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Pyrrolidine carboxylic acids / N-acylpyrrolidines / Aralkylamines / Fatty acid esters / Benzene and substituted derivatives / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Carboxylic acid esters / Amino acids / Dialkylamines / Carboxylic acids / Azacyclic compounds / Carbonyl compounds / Organic oxides / Organopnictogen compounds / Hydrocarbon derivatives

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Substituents

Alpha-amino acid amide / Alpha-amino acid ester / Alpha-amino acid or derivatives / Alpha-dipeptide / Amine / Amino acid / Amino acid or derivatives / Aralkylamine / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid / Carboxylic acid ester / Dicarboxylic acid or derivatives / Fatty acid ester / Fatty acyl / Hydrocarbon derivative / Monocyclic benzene moiety / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / N-acyl-l-alpha-amino acid / N-acylpyrrolidine / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organoheterocyclic compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Proline or derivatives / Pyrrolidine / Pyrrolidine carboxylic acid / Pyrrolidine carboxylic acid or derivatives / Secondary aliphatic amine / Secondary amine / Tertiary carboxylic acid amide

show 28 more

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

dicarboxylic acid monoester, dipeptide (CHEBI:4784)

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

69PN84IO1A

CAS number

75847-73-3

InChI Key

GBXSMTUPTTWBMN-XIRDDKMYSA-N

InChI

InChI=1S/C20H28N2O5/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25)/t14-,16-,17-/m0/s1

IUPAC Name

(2S)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid

SMILES

CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O

References

Synthesis Reference

K. S. Keshava Murthy, Andrew Burchat, Gamini Weeratunga, "Sodium enalapril complex and the use thereof to make sodium enalapril." U.S. Patent US5637730, issued February, 1983.

US5637730

General References

1. Swanson BN, Vlasses PH, Ferguson RK, Bergquist PA, Till AE, Irvin JD, Harris K: Influence of food on the bioavailability of enalapril. J Pharm Sci. 1984 Nov;73(11):1655-7. [Article]
2. Davies RO, Gomez HJ, Irvin JD, Walker JF: An overview of the clinical pharmacology of enalapril. Br J Clin Pharmacol. 1984;18 Suppl 2:215S-229S. [Article]
3. MacFadyen RJ, Meredith PA, Elliott HL: Enalapril clinical pharmacokinetics and pharmacokinetic-pharmacodynamic relationships. An overview. Clin Pharmacokinet. 1993 Oct;25(4):274-82. doi: 10.2165/00003088-199325040-00003. [Article]
4. Vlasses PH, Larijani GE, Conner DP, Ferguson RK: Enalapril, a nonsulfhydryl angiotensin-converting enzyme inhibitor. Clin Pharm. 1985 Jan-Feb;4(1):27-40. [Article]
5. Gomez HJ, Cirillo VJ, Irvin JD: Enalapril: a review of human pharmacology. Drugs. 1985;30 Suppl 1:13-24. doi: 10.2165/00003495-198500301-00004. [Article]
6. Todd PA, Heel RC: Enalapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1986 Mar;31(3):198-248. doi: 10.2165/00003495-198631030-00002. [Article]
7. Todd PA, Goa KL: Enalapril. A reappraisal of its pharmacology and therapeutic use in hypertension. Drugs. 1992 Mar;43(3):346-81. doi: 10.2165/00003495-199243030-00005. [Article]
8. Ulm EH, Hichens M, Gomez HJ, Till AE, Hand E, Vassil TC, Biollaz J, Brunner HR, Schelling JL: Enalapril maleate and a lysine analogue (MK-521): disposition in man. Br J Clin Pharmacol. 1982 Sep;14(3):357-62. doi: 10.1111/j.1365-2125.1982.tb01991.x. [Article]
9. 22. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 270-271). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
10. Enalapril Oral Tablets - Product Monograph [Link]
11. Angiotensin Converting Enzyme Inhibitors (ACEI) - StatPearls [Link]
12. FDA Approved Drug Products: VASOTEC (enalapril maleate) tablets [Link]
13. FDA Approved Drug Products: EPANED (enalapril maleate) solution [Link]
14. FDA Approved Drug Products: LEXXEL (enalapril maleate and felodipine) tablets [Link]
15. FDA Approved Drug Products: VASERETIC (enalapril maleate and hydrochlorothiazide) tablets [Link]

External Links

Human Metabolome Database

HMDB0014722

KEGG Drug

D07892

KEGG Compound

C06977

PubChem Compound

5388962

PubChem Substance

46507920

ChemSpider

4534998

BindingDB

50017129

RxNav

3827

ChEBI

4784

ChEMBL

CHEMBL578

ZINC

ZINC000003791297

Therapeutic Targets Database

DAP001374

PharmGKB

PA449456

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

PDRhealth

PDRhealth Drug Page

Wikipedia

Enalapril

FDA label

Download (120 KB)

MSDS

Download (173 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Screening	Healthy Subjects (HS)	1
4	Active Not Recruiting	Treatment	Chagas Disease / Heart Failure	1
4	Completed	Basic Science	Carboxylesterase 1 (CES1) Genotype / CES1 Activity	1
4	Completed	Basic Science	Coronavirus Disease 2019 (COVID‑19) / Myocarditis Allergic / Renal Dialysis / Severe Acute Respiratory Syndrome-related Coronavirus / Vaccines / Viral Infections	1
4	Completed	Basic Science	Hypertension / Syndrome, Metabolic	1

Pharmacoeconomics

Manufacturers

• Apotex inc
• Apothecon inc div bristol myers squibb
• 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 pharmaceuticals usa inc
• Watson laboratories inc
• Wockhardt americas inc
• Biovail laboratories international srl
• Bedford laboratories div ben venue laboratories inc
• Hikma farmaceutica (portugal) sa
• Hospira inc
• Teva parenteral medicines inc

Packagers

• Advanced Pharmaceutical Services Inc.
• Amerisource Health Services Corp.
• Apace Packaging
• Apotex Inc.
• Apotheca Inc.
• A-S Medication Solutions LLC
• Baxter International Inc.
• Bedford Labs
• Ben Venue Laboratories Inc.
• Bryant Ranch Prepack
• BTA Pharmaceuticals
• California Clinical Pharmacy Inc.
• Cardinal Health
• Comprehensive Consultant Services Inc.
• Corepharma LLC
• Coupler Enterprises Inc.
• Direct Dispensing Inc.
• Dispensing Solutions
• Diversified Healthcare Services Inc.
• Emcure Pharmaceuticals Ltd.
• Eon Labs
• Heartland Repack Services LLC
• Hikma Pharmaceuticals
• Hospira Inc.
• Ivax Pharmaceuticals
• Krka d.d. Novo Mesto
• Lake Erie Medical and Surgical Supply
• Lek Pharmaceuticals Inc.
• Major Pharmaceuticals
• Medisca Inc.
• Merck & Co.
• Merrell Pharmaceuticals Inc.
• Murfreesboro Pharmaceutical Nursing Supply
• Mylan
• Neuman Distributors Inc.
• Nucare Pharmaceuticals Inc.
• Ohm Laboratories Inc.
• Palmetto Pharmaceuticals Inc.
• Par Pharmaceuticals
• Patheon Inc.
• PCA LLC
• PD-Rx Pharmaceuticals Inc.
• Pharmaceutical Utilization Management Program VA Inc.
• Pharmedix
• Pharmpak Inc.
• Physicians Total Care Inc.
• Preferred Pharmaceuticals Inc.
• Prepackage Specialists
• Prepak Systems Inc.
• Ranbaxy Laboratories
• Rebel Distributors Corp.
• Remedy Repack
• Sandhills Packaging Inc.
• Sandoz
• Southwood Pharmaceuticals
• Taro Pharmaceuticals USA
• Teva Pharmaceutical Industries Ltd.
• Tya Pharmaceuticals
• UDL Laboratories
• Vangard Labs Inc.
• Watson Pharmaceuticals
• West-Ward Pharmaceuticals
• Wockhardt Ltd.

Dosage Forms

Form	Route	Strength
Tablet	Oral	10.000 mg
Tablet	Oral	2.5 mg
Tablet	Oral	20.000 mg
Tablet	Oral	10.0 mg
Tablet	Oral	20.0 mg
Tablet	Oral	5.0 mg
Powder, for suspension	Oral	0.006 g
Tablet	Oral	5.254 mg
Capsule, coated	Oral
Tablet	Oral	30 MG
Tablet	Oral	40 MG
Tablet	Oral	2 mg / tab
Tablet	Oral	2000000 mg
Tablet, film coated	Oral	5 mg
Tablet	Oral	5.1 mg
Tablet	Oral	500000 mg
Tablet, coated	Oral
Tablet	Oral	10 mg/1
Tablet	Oral	2.5 mg/1
Tablet	Oral	20 mg/1
Tablet	Oral	5 mg/1
Tablet, soluble	Oral	10 mg/1
Tablet, soluble	Oral	2.5 mg/1
Tablet, soluble	Oral	20 mg/1
Tablet, soluble	Oral	5 mg/1
Tablet	Oral
Tablet	Oral	20.4 mg
Tablet, film coated	Oral
Tablet	Oral
Tablet	Oral	10 MG
Tablet	Oral	5.000 mg
Tablet	Oral	10.00 MG
Solution	Oral	1 mg/1mL
Tablet	Oral	5.00 mg
Tablet, extended release	Oral
Tablet	Oral	48.31 mg
Tablet	Oral	32 mg
Tablet	Oral	4.0 mg
Tablet	Oral	8.0 mg
Tablet	Oral	2 mg
Tablet	Oral	16 mg
Tablet	Oral	2.0 mg
Tablet	Oral	4 mg
Tablet	Oral	8 mg
Tablet	Oral	20 mg
Tablet	Oral	5 mg
Tablet, coated	Oral	20 mg

Prices

Unit description	Cost	Unit
Enalapril maleate powder	9.18USD	g
Enalaprilat 1.25 mg/ml vial	3.6USD	ml
Vasotec 20 mg tablet	3.36USD	tablet
Vaseretic 10-25 mg tablet	3.15USD	tablet
Vasotec 10 mg tablet	2.63USD	tablet
Vasotec 5 mg tablet	2.08USD	tablet
Vasotec 2.5 mg tablet	1.65USD	tablet
Enalapril maleate 20 mg tablet	1.56USD	tablet
Vaseretic 5-12.5 mg tablet	1.49USD	tablet
Vasotec 20 mg Tablet	1.34USD	tablet
Vasotec 10 mg Tablet	1.11USD	tablet
Enalapril maleate 10 mg tablet	1.09USD	tablet
Enalapril maleate 5 mg tablet	1.03USD	tablet
Vasotec 5 mg Tablet	0.92USD	tablet
Enalapril maleate 2.5 mg tablet	0.82USD	tablet
Vasotec 2.5 mg Tablet	0.78USD	tablet
Apo-Enalapril 20 mg Tablet	0.75USD	tablet
Co Enalapril 20 mg Tablet	0.75USD	tablet
Mylan-Enalapril 20 mg Tablet	0.75USD	tablet
Novo-Enalapril 20 mg Tablet	0.75USD	tablet
Pms-Enalapril 20 mg Tablet	0.75USD	tablet
Ratio-Enalapril 20 mg Tablet	0.75USD	tablet
Sandoz Enalapril 20 mg Tablet	0.75USD	tablet
Taro-Enalapril 20 mg Tablet	0.75USD	tablet
Apo-Enalapril 10 mg Tablet	0.62USD	tablet
Co Enalapril 10 mg Tablet	0.62USD	tablet
Mylan-Enalapril 10 mg Tablet	0.62USD	tablet
Novo-Enalapril 10 mg Tablet	0.62USD	tablet
Pms-Enalapril 10 mg Tablet	0.62USD	tablet
Ratio-Enalapril 10 mg Tablet	0.62USD	tablet
Sandoz Enalapril 10 mg Tablet	0.62USD	tablet
Taro-Enalapril 10 mg Tablet	0.62USD	tablet
Apo-Enalapril 5 mg Tablet	0.52USD	tablet
Co Enalapril 5 mg Tablet	0.52USD	tablet
Mylan-Enalapril 5 mg Tablet	0.52USD	tablet
Novo-Enalapril 5 mg Tablet	0.52USD	tablet
Pms-Enalapril 5 mg Tablet	0.52USD	tablet
Ratio-Enalapril 5 mg Tablet	0.52USD	tablet
Sandoz Enalapril 5 mg Tablet	0.52USD	tablet
Taro-Enalapril 5 mg Tablet	0.52USD	tablet
Apo-Enalapril 2.5 mg Tablet	0.44USD	tablet
Co Enalapril 2.5 mg Tablet	0.44USD	tablet
Mylan-Enalapril 2.5 mg Tablet	0.44USD	tablet
Novo-Enalapril 2.5 mg Tablet	0.44USD	tablet
Pms-Enalapril 2.5 mg Tablet	0.44USD	tablet
Ratio-Enalapril 2.5 mg Tablet	0.44USD	tablet
Sandoz Enalapril 2.5 mg Tablet	0.44USD	tablet
Taro-Enalapril 2.5 mg Tablet	0.44USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US8778366	No	2014-07-15	2032-11-06
US8568747	No	2013-10-29	2032-11-06
US9669008	No	2017-06-06	2036-03-25
US9808442	No	2017-11-07	2036-03-25
US9855214	No	2018-01-02	2032-11-06
US9968553	No	2018-05-15	2032-11-06
US10039745	No	2018-08-07	2036-03-25
US10154987	No	2018-12-18	2036-03-25
US10772868	No	2020-09-15	2036-03-25
US10786482	No	2020-09-29	2036-03-25
US11040023	No	2021-06-22	2036-03-25
US11141405	No	2021-10-12	2036-03-25
US11173141	No	2021-11-16	2036-03-25

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	143-144.5	MSDS
water solubility	1.64E+004 mg/L	MCFARLAND,JW ET AL. (2001)
logP	0.07	HANSCH,C ET AL. (1995)
Caco2 permeability	-5.64	ADME Research, USCD

Predicted Properties

Property	Value	Source
Water Solubility	0.213 mg/mL	ALOGPS
logP	0.19	ALOGPS
logP	0.59	Chemaxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	3.67	Chemaxon
pKa (Strongest Basic)	5.2	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	5	Chemaxon
Hydrogen Donor Count	2	Chemaxon
Polar Surface Area	95.94 Å2	Chemaxon
Rotatable Bond Count	10	Chemaxon
Refractivity	99.57 m3·mol-1	Chemaxon
Polarizability	40.41 Å3	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.7428
Blood Brain Barrier	-	0.9659
Caco-2 permeable	-	0.8956
P-glycoprotein substrate	Substrate	0.7691
P-glycoprotein inhibitor I	Non-inhibitor	0.6681
P-glycoprotein inhibitor II	Non-inhibitor	0.5136
Renal organic cation transporter	Non-inhibitor	0.8442
CYP450 2C9 substrate	Non-substrate	0.8632
CYP450 2D6 substrate	Non-substrate	0.9116
CYP450 3A4 substrate	Non-substrate	0.5696
CYP450 1A2 substrate	Non-inhibitor	0.9125
CYP450 2C9 inhibitor	Non-inhibitor	0.9154
CYP450 2D6 inhibitor	Non-inhibitor	0.9231
CYP450 2C19 inhibitor	Non-inhibitor	0.9025
CYP450 3A4 inhibitor	Non-inhibitor	0.8309
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.6825
Ames test	Non AMES toxic	0.9383
Carcinogenicity	Non-carcinogens	0.9216
Biodegradation	Not ready biodegradable	0.8686
Rat acute toxicity	1.8269 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9719
hERG inhibition (predictor II)	Non-inhibitor	0.7456

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0udi-4329000000-0ccc991d6f82c8023381
LC-MS/MS Spectrum - LC-ESI-QFT , negative	LC-MS/MS	splash10-004i-0809000000-0e192d1573028e60641c
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-003r-1859000000-8b202071e8860792a59f
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-056r-0329000000-831478ce8de7741826a0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-004i-0249000000-1fa4c3835837163595b7
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03dl-6923000000-531b7bd3fc250f143a49
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-08i3-2933000000-b16ec6c5a3d022c07ebe
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-03di-2911000000-97697e1a52f2fea8031f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-06r6-6911000000-f2027429f1a90f09ec98
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	208.51317	predicted	DarkChem Lite v0.1.0
[M-H]-	209.17627	predicted	DarkChem Lite v0.1.0
[M-H]-	187.60167	predicted	DeepCCS 1.0 (2019)
[M+H]+	207.21777	predicted	DarkChem Lite v0.1.0
[M+H]+	210.04177	predicted	DarkChem Lite v0.1.0
[M+H]+	189.95967	predicted	DeepCCS 1.0 (2019)
[M+Na]+	208.05917	predicted	DarkChem Lite v0.1.0
[M+Na]+	209.58057	predicted	DarkChem Lite v0.1.0
[M+Na]+	196.05284	predicted	DeepCCS 1.0 (2019)

Targets

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Binding Properties

×

Property	Measurement	pH	Temperature (°C)	References
IC 50 (nM)	140	N/A	N/A	A28630 / A28633 / A13432
IC 50 (nM)	1273	N/A	N/A	A28631
IC 50 (nM)	8000	N/A	N/A	A28632
IC 50 (nM)	4.5	N/A	N/A	A28634 / A27344
IC 50 (nM)	2	N/A	N/A	A28538
IC 50 (nM)	1200	N/A	N/A	A28635

Details

Binding Properties1. Angiotensin-converting enzyme

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Zinc ion binding

Specific Function

Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...

Gene Name

ACE

Uniprot ID

P12821

Uniprot Name

Angiotensin-converting enzyme

Molecular Weight

149713.675 Da

References

1. Andujar-Sanchez M, Jara-Perez V, Camara-Artigas A: Thermodynamic determination of the binding constants of angiotensin-converting enzyme inhibitors by a displacement method. FEBS Lett. 2007 Jul 24;581(18):3449-54. Epub 2007 Jun 27. [Article]
2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
3. Liu YH, Liu LY, Wu JX, Chen SX, Sun YX: Comparison of captopril and enalapril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE inhibitors in high dieted methionine mice. J Cardiovasc Pharmacol. 2006 Jan;47(1):82-8. [Article]
4. Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR: Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. [Article]

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Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55