Chemical: Drug
perindopril

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1. FDA Label for perindopril

Full label available at DailyMed

Genes and/or phenotypes found in this label


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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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.

List of all variant annotations for perindopril

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs12050217 NC_000014.8:g.96728753A>G, NC_000014.9:g.96262416A>G, NM_000710.3:c.-129-236A>G, XM_005267977.1:c.-10-1257A>G, XM_005267978.1:c.-129-236A>G, rs33949564, rs36221127, rs58745600
A > G
SNP
No VIP available No Clinical Annotations available VA
rs1799722 NC_000014.8:g.96671139C>T, NC_000014.9:g.96204802C>T, NM_000623.3:c.-192C>T, XM_005267979.1:c.-197C>T, XM_005267980.1:c.-2965C>T, XM_005267981.1:c.-439C>T, rs60242377
C > T
SNP
No VIP available CA VA
rs1799752 NC_000017.10:g.61565890_61565891insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NC_000017.10:g.61565890_61565891insG, NC_000017.11:g.63488529_63488530insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NC_000017.11:g.63488529_63488530insG, NG_011648.1:g.16457_16458insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NG_011648.1:g.16457_16458insG, NM_000789.3:c.2306-119_2306-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_000789.3:c.2306-119_2306-118insG, NM_001178057.1:c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_001178057.1:c.584-119_584-118insG, NM_152830.2:c.584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, NM_152830.2:c.584-119_584-118insG, XM_005257110.1:c.1757-119_1757-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, XM_005257110.1:c.1757-119_1757-118insG, XM_006721737.2:c.644-119_644-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, XM_006721737.2:c.644-119_644-118insG
- > ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC
- > G
indel
No VIP available CA VA
rs275651 NC_000003.11:g.148414887T>A, NC_000003.12:g.148697100T>A, NG_008468.1:g.4230T>A, NM_000685.4:c.-1159T>A, NM_004835.4:c.-1028T>A, NM_009585.3:c.-1075T>A, NM_031850.3:c.-1112T>A, rs111181444, rs17230455, rs1800768, rs3755646, rs60031984, rs61174253, rs770424, rs770637
T > A
SNP
No VIP available CA VA
rs5182 NC_000003.11:g.148459395C>T, NC_000003.12:g.148741608C>T, NG_008468.1:g.48738C>T, NM_000685.4:c.573C>T, NM_004835.4:c.678C>T, NM_009585.3:c.573C>T, NM_031850.3:c.678C>T, NM_032049.3:c.660C>T, NP_000676.1:p.Leu191=, NP_004826.5:p.Leu226=, NP_033611.1:p.Leu191=, NP_114038.4:p.Leu226=, NP_114438.2:p.Leu220=, rs17231259, rs17845691, rs17858633, rs275648, rs3772606, rs56755191
C > T
SNP
L191L
No VIP available CA VA
rs5186 NC_000003.11:g.148459988A>C, NC_000003.12:g.148742201A>C, NG_008468.1:g.49331A>C, NM_000685.4:c.*86A>C, NM_004835.4:c.*86A>C, NM_009585.3:c.*86A>C, NM_031850.3:c.*86A>C, NM_032049.3:c.*86A>C, rs17231380, rs3192044, rs3732563, rs386597902, rs59796105
A > C
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Perindopril Erbumine
Trade Names
  • Aceon
  • Coversyl
Brand Mixture Names
  • Coversyl Plus (Indapamide + Perindopril Erbumine)
  • Preterax (Indapamide + Perindopril Erbumine)

PharmGKB Accession Id

PA450877

Type(s):

Drug

Description

Perindopril is a nonsulfhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to perindoprilat, its active metabolite, following oral administration. Perindoprilat 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). Perindopril may be used to treat mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease.

Source: Drug Bank

Indication

For the treatment of mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease.

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. Perindoprilat, the active metabolite of perindopril, 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. Perindopril 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

Perindopril is a nonsulfhydryl prodrug that is metabolized via first pass effect (62%) and systemic hydrolysis (38%) to perindoprilat, its active metabolite, following oral administration. Perindoprilat 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 perindoprilat by causing increased vasodilation and decreased blood pressure.

Source: Drug Bank

Food Interaction

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

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Extensively metabolized, with only 4-12% of the dose recovered in urine following oral administration. Six metabolites have been identified: perindoprilat, perindopril glucuronide, perindoprilat glucuronide, a perindopril lactam, and two perindoprilat lactams. Only perindoprilat is pharmacologically active. Peridoprilat and perindoprilat glucuronide are the two main circulating metabolites.

Source: Drug Bank

Protein Binding

Perindoprilat, 10-20% bound to plasma proteins

Source: Drug Bank

Absorption

Rapidly absorbed with peak plasma concentrations occurring approximately 1 hour after oral administration. Bioavailability is 65-75%. Following absorption, perindopril is hydrolyzed to perindoprilat, which has an average bioavailability of 20%. The rate and extent of absorption is unaffected by food. However, food decreases the extent of biotransformation to peridoprilat and reduces its bioavailability by 35%.

Source: Drug Bank

Half-Life

Perindopril, 1.2 hours; Peridoprilat, 30-120 hours. The long half life of peridoprilat is due to its slow dissociation from ACE binding sites.

Source: Drug Bank

Toxicity

The most likely symptom of overdose is severe hypotension. The most common adverse effects observed in controlled clinical trials include cough, digestive symptoms, fatigue, headache, and dizziness.

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

Perindopril is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine.

Source: Drug Bank

Chemical Properties

Chemical Formula

C19H32N2O5

Source: Drug Bank

Isomeric SMILES

CCC[C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@H]2CCCC[C@H]2C[C@H]1C(=O)O

Source: OpenEye

Canonical SMILES

CCC[C@H](N[C@@H]

Source: Drug Bank

Average Molecular Weight

368.4678

Source: Drug Bank

Monoisotopic Molecular Weight

368.231122144

Source: Drug Bank

SMILES

[H][C@]12C[C@H](N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O

Source: Drug Bank

InChI String

InChI=1S/C19H32N2O5/c1-4-8-14(19(25)26-5-2)20-12(3)17(22)21-15-10-7-6-9-13(15)11-16(21)18(23)24/h12-16,20H,4-11H2,1-3H3,(H,23,24)/t12-,13-,14-,15-,16-/m0/s1

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)
IAPP (source: Drug Bank)

Drug Interactions

Interaction Description
amiloride - perindopril Increased risk of hyperkaliemia (source: Drug Bank)
amiloride - perindopril Increased risk of hyperkaliemia (source: Drug Bank)
lithium - perindopril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
lithium - perindopril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
perindopril - amiloride Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - amiloride Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - drospirenone Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - lithium The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
perindopril - lithium The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
perindopril - potassium Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - potassium Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - spironolactone Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - spironolactone Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
perindopril - tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
perindopril - triamterene Increased risk of hyperkaliemia (source: Drug Bank)
perindopril - triamterene Increased risk of hyperkaliemia (source: Drug Bank)
tizanidine - perindopril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
tizanidine - perindopril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
treprostinil - perindopril Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank)
triamterene - perindopril Increased risk of hyperkaliemia (source: Drug Bank)
triamterene - perindopril 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 perindopril: 10

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Individualized Angiotensin-Converting Enzyme (ACE)-Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model. Journal of the American Heart Association. 2016. Oemrawsingh Rohit 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
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 CA VA No VIP available No VIP available
Tailored therapy of ACE inhibitors in stable coronary artery disease: pharmacogenetic profiling of treatment benefit. Pharmacogenomics. 2010. Brugts Jasper J, 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
The rationale and design of the PERindopril GENEtic association study (PERGENE): a pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. 2009. Brugts J J, 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
Reduction in arterial stiffness with angiotensin II antagonism and converting enzyme inhibition. A comparative study among malay hypertensive subjects with a known genetic profile. American journal of hypertension. 2007. Rehman Asia, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A study of the relationships between angiotensin- converting enzyme gene, chymase gene polymorphisms, pharmacological treatment with ACE inhibitor and regression of left ventricular hypertrophy in essential hypertension patients treated with benazepril. Annals of human biology. 2005. He Hong, 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
The ACE gene I/D polymorphism is not associated with the blood pressure and cardiovascular benefits of ACE inhibition. Hypertension. 2003. Harrap Stephen B, 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 insertion/deletion, not bradykinin B2 receptor -58T/C gene polymorphism, associated with angiotensin-converting enzyme inhibitor-related cough in Chinese female patients with non-insulin-dependent diabetes mellitus. Metabolism: clinical and experimental. 2001. Lee Y J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2000. Ha S K, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Influence of the angiotensin II type 1 receptor gene polymorphism on the effects of perindopril and nitrendipine on arterial stiffness in hypertensive individuals. Hypertension. 1996. Benetos A, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0032-1101-01
DrugBank:
DB00790
ChEBI:
8024
8025
KEGG Compound:
C07706
C07707
KEGG Drug:
D00624
D03753
PubChem Compound:
107807
PubChem Substance:
46508767
Drugs Product Database (DPD):
2246624
ChemSpider:
96956
Therapeutic Targets Database:
DNC001114
FDA Drug Label at DailyMed:
c9d01204-2789-40d0-93e9-e4cf018e8226

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.