Drug/Small Molecule:
ramipril

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 has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

Links to Unannotated Labels

These links are to labels associated with ramipril that have not been annotated by PharmGKB.

  1. DailyMed - DrugLabel PA166105234

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 No Clinical Annotations available VA
rs4344 17291G>A, 2641+231G>A, 26840876G>A, 61566724G>A, 919+231G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs4359 1658+512T>C, 22910T>C, 26846495T>C, 3380+512T>C, 61572343T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs4363 1847-6G>A, 1970-6G>A, 25059G>A, 26848644G>A, 3692-6G>A, 61574492G>A
G > A
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Ramiprilum [Latin]
Trade Names
  • Acovil
  • Altace
  • Carasel
  • Cardace
  • Delix
  • Hypren
  • Hytren
  • Lostapres
  • Pramace
  • Quark
  • Ramace
  • Triatec
  • Tritace
  • Unipril
  • Vesdil
Brand Mixture Names

PharmGKB Accession Id:
PA451223

Description

Ramipril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to ramiprilat in the liver and, to a lesser extent, kidneys. Ramiprilat 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). Ramipril may be used in the treatment of hypertension, congestive heart failure, nephropathy, and to reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events.

Source: Drug Bank

Indication

For the management of mild to severe hypertension. May be used to reduce cardiovascular mortality following myocardial infarction in hemodynamically stable individuals who develop clinical signs of congestive heart failure within a few days following myocardial infarction. To reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events. May be used to slow the progression of renal disease in individuals with hypertension, diabetes mellitus and microalubinuria or overt nephropathy.

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. Ramiprilat, the principle active metabolite of ramipril, 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. Ramipril 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.

Source: Drug Bank

Pharmacology

Ramipril is an ACE inhibitor similar to benazepril, fosinopril and quinapril. It is an inactive prodrug that is converted to ramiprilat in the liver, the main site of activation, and kidneys. Ramiprilat confers blood pressure lowing effects 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 ramiprilat by causing increased vasodilation and decreased blood pressure.

Source: Drug Bank

Food Interaction

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

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic metabolism accounts for 75% of total ramipril metabolism. 25% of hepatic metabolism produces the active metabolite ramiprilat via liver esterase enzymes. 100% of renal metabolism converts ramipril to ramiprilat. Other metabolites, diketopiperazine ester, the diketopiperazine acid, and the glucuronides of ramipril and ramiprilat, are inactive.

Source: Drug Bank

Protein Binding

Protein binding of ramipril is about 73% and that of ramiprilat about 56%.

Source: Drug Bank

Absorption

The extent of absorption is at least 50-60%. Food decreases the rate of absorption from the GI tract without affecting the extent of absorption. The absolute bioavailabilities of ramipril and ramiprilat were 28% and 44%, respectively, when oral administration was compared to intravenous administration.

Source: Drug Bank

Half-Life

Plasma concentrations of ramiprilat decline in a triphasic manner. Initial rapid decline represents distribution into tissues and has a half life of 2-4 hours. The half life of the apparent elimination phase is 9-18 hours and that of the terminal elimination phase is > 50 hours. Two elimination phases occur as a result of ramiprilat's potent binding to ACE and slow dissociation from the enzyme. The half life of ramiprilat after multiple daily doses (MDDs) is dose-dependent, ranging from 13-17 hours with 5-10 mg MDDs to 27-36 hours for 2.5 mg MDDs.

Source: Drug Bank

Toxicity

Symptoms of overdose may include excessive peripheral vasodilation (with marked hypotension and shock), bradycardia, electrolyte disturbances, and renal failure. The most likely adverse reactions are symptoms attributable to its blood-pressure lowing effect. May cause headache, dizziness, asthenia, chest pain, nausea, peripheral edema, somnolence, impotence, rash, arthritis, and dyspnea.
LD 50 = 10933 mg/kg (orally in mice).

Source: Drug Bank

Chemical Properties

Chemical Formula

C23H32N2O5

Source: Drug Bank

Isomeric SMILES

CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)N2[C@H]3CCC[C@H]3C[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

416.5106

Source: Drug Bank

Monoisotopic Molecular Weight

416.231122144

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 ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ACE

Drug Targets

Gene Description
ACE (source: Drug Bank)

Drug Interactions

Drug Description
ramipril Increased risk of hyperkaliemia (source: Drug Bank)
ramipril Increased risk of hyperkaliemia (source: Drug Bank)
ramipril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
ramipril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
ramipril Increased risk of hyperkaliemia (source: Drug Bank)
ramipril 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)
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)
ramipril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
ramipril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
ramipril Increased risk of nephrotoxicity (source: Drug Bank)
ramipril Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank)
ramipril Increased risk of hyperkaliemia (source: Drug Bank)
ramipril 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 ramipril: 3

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, 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
Telmisartan, ramipril, or both in patients at high risk for vascular events. The New England journal of medicine. 2008. ONTARGET Investigators, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial. Journal of hypertension. 2007. Bhatnagar Vibha, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
54868-5896-0
DrugBank:
DB00178
ChEBI:
8774
KEGG Drug:
D00421
PubChem Compound:
5362129
PubChem Substance:
193088
46506390
Drugs Product Database (DPD):
2221829
ChemSpider:
4514937
Therapeutic Targets Database:
DAP000581
FDA Drug Label at DailyMed:
9d008401-4746-4dc5-94ab-4462f959fb73

Clinical Trials

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

Common Searches

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