Drug/Small Molecule:
enalapril

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB contains no drug labels with pharmacogenomic information for this drug/small molecule. To report a drug label with PGx, click here.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs1042714 148206473G>C, 148206473G>G, 318C>G, 5318C>G, 79C>G, 9369400G>C, 9369400G>G, ADRB2:27Glu>Gln, ADRB2:79C>G, ADRB2:Gln27Glu, Gln27
G > C
Missense
Gln27Glu
No VIP available No Clinical Annotations available VA
rs12683493 105584C>T, 136155063C>T, 2932003C>T
C > T
Not Available
No VIP available No Clinical Annotations available VA
rs1799722 -192C>T, -58, 77671139C>T, 96671139C>T, BDKRB2 C-58T, BDRKRB2:
C > T
5' UTR
rs1799752 16457_16458insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 2306-119_2306-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 26840042_26840043insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 61565890_61565891insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, ACE D/I
- > ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC
Intronic
No VIP available No Clinical Annotations available VA
rs1799983 11291734T>G, 12965T>G, 150696111T>G, 894T>G, Asp298Glu, NOS3:894G>T
T > G
Missense
Asp298Glu
No VIP available No Clinical Annotations available VA
rs2070744 -51-762C>T, -786, -813C>T, 11285702C>T, 150690079C>T, 6933C>T, NOS3 -786T>C, NOS3:, T>C, eNOS -786T>C
C > T
5' Flanking
No VIP available No Clinical Annotations available VA
rs2070950 -2-358C>G, 10301C>G, 149358372G>C, 73906093G>C
G > C
Intronic
VIP No Clinical Annotations available No Variant Annotations available
rs2306283 14089862A>G, 21329738A>G, 388A>G, 50611A>G, Asn130Asp, SLCO1B1*1B
A > G
Missense
Asn130Asp
VIP No Clinical Annotations available No Variant Annotations available
rs4149015 -910G>A, 14043446G>A, 21283322G>A, 4195G>A, SLCO1B1:11187G>A, SLCO1B1:G-11187A
G > A
5' Flanking
VIP No Clinical Annotations available No Variant Annotations available
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
No VIP available No Clinical Annotations available VA
rs495828 105388T>T, 136154867G>T, 2931807G>T, Marker for A antigen allele, rs495828 C>A
T > G
Not Available
No VIP available CA VA
rs5522 11198G>A, 149357475C>T, 538G>A, 73905196C>T, Val180Ile
C > T
Missense
Val180Ile
No VIP available No Clinical Annotations available VA
rs61722009
A > 3
A > (AGGGGTGAGGAAGTCTAGACCTGCTGC)2
Not Available
No VIP available No Clinical Annotations available VA
rs8176740 136131472A>T, 21583T>A, 2908412A>T, 646T>A, 82178A>T, Phe216Ile
A > T
Missense
Phe216Ile
No VIP available No Clinical Annotations available VA
rs8176746 136131322G>T, 21733C>A, 2908262G>T, 796C>A, 82028G>T, Leu266Met, Marker for B antigen allele, rs8176746 C>A
G > T
Missense
Leu266Met
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Enalapril Maleate
  • Enalaprila [INN-Spanish]
  • Enalaprilat
  • Enalaprilum [INN-Latin]
Trade Names
  • Bonuten
  • Enalapril Bp
  • Enalapril Richet
  • Gadopril
  • Kinfil
  • Vaseretic
  • Vasotec
  • Vasotec IV
Brand Mixture Names
  • Vaseretic (Enalapril Maleate + Hydrochlorothiazide)

PharmGKB Accession Id:
PA449456

Description

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.

Source: Drug Bank

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.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

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.

Source: Drug Bank

Pharmacology

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.

Source: Drug Bank

Food Interaction

Herbs that may attenuate the antihypertensive effect of enalapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.|Enalapril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.|High salt intake may attenuate the antihypertensive effect of enalapril.|Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

~ 60% of absorbed dose is extensively hydrolyzed to enalaprilat, primarily by liver esterases

Source: Drug Bank

Protein Binding

50-60% of enalaprilat is bound to plasma proteins

Source: Drug Bank

Absorption

55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity.

Source: Drug Bank

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.

Source: Drug Bank

Toxicity

Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue.

Source: Drug Bank

Route of Elimination

Excretion of enalapril is primarily renal.

Source: Drug Bank

Chemical Properties

Chemical Formula

C20H28N2O5

Source: Drug Bank

Isomeric SMILES

CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)O

Source: OpenEye

Canonical SMILES

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

Source: Drug Bank

Average Molecular Weight

376.4467

Source: Drug Bank

Monoisotopic Molecular Weight

376.199822016

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ACE (source: Drug Bank)

Drug Interactions

Drug Description
enalapril Increased risk of hyperkaliemia (source: Drug Bank)
enalapril Increased risk of hyperkaliemia (source: Drug Bank)
amiloride Increased risk of hyperkaliemia (source: Drug Bank)
amiloride Increased risk of hyperkaliemia (source: Drug Bank)
drospirenone Increased risk of hyperkaliemia (source: Drug Bank)
lithium The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
lithium The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
potassium Increased risk of hyperkaliemia (source: Drug Bank)
potassium Increased risk of hyperkaliemia (source: Drug Bank)
rifampin Rifampin reduces the efefct of enalapril (source: Drug Bank)
rifampin Rifampin reduces the efefct of enalapril (source: Drug Bank)
spironolactone Increased risk of hyperkaliemia (source: Drug Bank)
spironolactone Increased risk of hyperkaliemia (source: Drug Bank)
tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
triamterene Increased risk of hyperkaliemia (source: Drug Bank)
triamterene Increased risk of hyperkaliemia (source: Drug Bank)
enalapril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
enalapril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
enalapril Increased risk of hyperkaliemia (source: Drug Bank)
enalapril Increased risk of hyperkaliemia (source: Drug Bank)
enalapril Rifampin decreases the effect of enalapril (source: Drug Bank)
enalapril Rifampin decreases the effect of enalapril (source: Drug Bank)
enalapril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
enalapril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
enalapril Increased risk of nephrotoxicity (source: Drug Bank)
enalapril Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank)
enalapril Increased risk of hyperkaliemia (source: Drug Bank)
enalapril Increased risk of hyperkaliemia (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
May Prevent
Contraindicated With

Publications related to enalapril: 23

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Rs495828 polymorphism of the ABO gene is a predictor of enalapril-induced cough in Chinese patients with essential hypertension. Pharmacogenetics and genomics. 2014. Luo Jian-Quan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of NR3C2 genetic polymorphisms on the blood pressure response to enalapril treatment. Pharmacogenomics. 2014. Luo Jian-Quan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Personalizing the management of heart failure in congenital heart disease: challenges and opportunities. Pharmacogenomics. 2014. de Denus Simon, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
eNOS and BDKRB2 genotypes affect the antihypertensive responses to enalapril. European journal of clinical pharmacology. 2013. Silva P S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Combination antihypertensive treatment: is initiation order important?. Journal of clinical hypertension (Greenwich, Conn.). 2010. Gums John G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenetics and genomics. 2010. Oshiro Connie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
PharmGKB summary: very important pharmacogene information for angiotensin-converting enzyme. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Medicinal Chemistry of Drugs used in Diabetic Cardiomyopathy. Current medicinal chemistry. 2009. Adeghate E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
High dose Losartan and ACE gene polymorphism in IgA nephritis. Genomic medicine. 2008. Woo Keng-Thye, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Interaction between polymorphisms in the renin-angiotensin-system and angiotensin-converting enzyme inhibitor or beta-blocker use and the risk of myocardial infarction and stroke. The pharmacogenomics journal. 2008. Schelleman H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Xenobiotic transporters of the human organic anion transporting polypeptides (OATP) family. Xenobiotica; the fate of foreign compounds in biological systems. 2008. Hagenbuch B, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Beta2-adrenergic receptor polymorphisms and treatment-induced regression of left ventricular hypertrophy in hypertension. Clinical pharmacology and therapeutics. 2006. Iaccarino Guido, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Vectorial transport of enalapril by Oatp1a1/Mrp2 and OATP1B1 and OATP1B3/MRP2 in rat and human livers. The Journal of pharmacology and experimental therapeutics. 2006. Liu Lichuan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Comparison of the effect of enalapril and losartan in conjunction with surgical coronary revascularisation versus revascularisation alone on systemic endothelial function. Heart (British Cardiac Society). 2005. Trevelyan J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of quinapril, quinapril-hydrochlorothiazide, and enalapril on the bone mass of hypertensive subjects: relationship with angiotensin converting enzyme polymorphisms. American journal of hypertension. 2003. Pérez-Castrillón José L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association of polymorphisms of the renin-angiotensin system and bradykinin B2 receptor with ACE-inhibitor-related cough. Journal of human hypertension. 2002. Mukae S, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Insertion-deletion polymorphism of the ACE gene modulates reversibility of endothelial dysfunction with ACE inhibition. Circulation. 2000. Prasad A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Angiotensin-converting enzyme gene polymorphism determines the antiproteinuric and systemic hemodynamic effect of enalapril in patients with proteinuric renal disease. Austrian Study Group of the Effects of Enalapril Treatment in Proteinuric Renal Disease. Kidney & blood pressure research. 1998. Haas M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Bradykinin-induced vasodilation of human coronary arteries in vivo: role of nitric oxide and angiotensin-converting enzyme. Journal of the American College of Cardiology. 1997. Kuga T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Angiotensin converting enzyme insertion/deletion polymorphism and short-term renal response to ACE inhibition: role of sodium status. Kidney international. Supplement. 1997. van der Kleij F G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Relationship between the angiotensin converting enzyme gene polymorphism and the effects of enalapril on left ventricular hypertrophy and impaired diastolic filling in essential hypertension: M-mode and pulsed Doppler echocardiographic studies. Journal of hypertension. 1996. Sasaki M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy. Lancet. 1996. van Essen G G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy. The Journal of clinical investigation. 1995. Yoshida H, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-1051-01
DrugBank:
DB00584
PDB:
EAL
ChEBI:
4784
KEGG Compound:
C06977
PubChem Compound:
5362032
PubChem Substance:
191211
Drugs Product Database (DPD):
2019906
HET:
EAL
Therapeutic Targets Database:
DAP001374
FDA Drug Label at DailyMed:
bad08ec8-7f9e-47b6-83b9-437e0191080f

Clinical Trials

These are trials that mention enalapril and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.