Drug/Small Molecule:
captopril

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 captopril that have not been annotated by PharmGKB.

  1. DailyMed - DrugLabel PA166105084

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.

List of all captopril variant annotations

Gene ? Variant?
(142)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
rs1799752 16457_16458insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 2306-119_2306-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 26840042_26840043insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 584-119_584-118insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, 61565890_61565891insATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC, ACE D/I
- > ATACAGTCACTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCC
Intronic
No VIP available CA VA
rs2106809 13499823A>G, 15618061A>G, 186+788T>C, 7132T>C
A > G
Intronic
No VIP available CA VA
rs5186 *86A>C, 148459988A>C, 49331A>C, 54955134A>C, AGTR1:1166A/C, AGTR1:1166A>C, AGTR1:116A>C, AGTR1:A1166C, AT, R A1166C, angiotensin II type 1 receptor A1166C
A > C
3' UTR
No VIP available No Clinical Annotations available VA
rs699 230845794A>G, 24363573A>G, 803T>C, 9543T>C, AGT M235T, AGT Met235Thr, AGT:Met235Thr, angiotensinogen M235T
A > G
Missense
Met268Thr
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 142
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Captoprilum [INN-Latin]
  • Captopryl
  • L-Captopril
Trade Names
  • Acediur
  • Aceplus
  • Acepress
  • Acepril
  • Alopresin
  • Apopril
  • Capoten
  • Captolane
  • Captoril
  • Cesplon
  • Dilabar
  • Garranil
  • Hipertil
  • Hypertil
  • Lopirin
  • Lopril
  • Tenosbon
  • Tensobon
  • Tensoprel
Brand Mixture Names

PharmGKB Accession Id:
PA448780

Description

Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (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). Captopril may be used in the treatment of hypertension.

Source: Drug Bank

Indication

For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, beta-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic 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. Captopril, one of the few ACE inhibitors that is not a prodrug, 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. Captopril 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. Captopril's affinity for ACE is approximately 30,000 times greater than that of ATI.

Source: Drug Bank

Pharmacology

Captopril, an ACE inhibitor, antagonizes 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 its effects by causing increased vasodilation and decreased blood pressure.

Source: Drug Bank

Food Interaction

Herbs that may attenuate the antihypertensive effect of captopril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.|Captopril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.|High salt intake may attenuate the antihypertensive effect of captopril.|Food decreases absorption by 25 - 40%. Clinical significance is debatable.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Major metabolites are captopril-cysteine disulfide and the disulfide dimer of captopril. Metabolites may undergo reversible interconversion.

Source: Drug Bank

Protein Binding

25-30% bound to plasma proteins, primarily albumin

Source: Drug Bank

Absorption

60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)

Source: Drug Bank

Half-Life

2 hours

Source: Drug Bank

Toxicity

Symptoms of overdose include emesis and decreased blood pressure. Side effects include dose-dependent rash (usually maculopapular), taste alterations, hypotension, gastric irritation, cough, and angioedema.

Source: Drug Bank

Chemical Properties

Chemical Formula

C9H15NO3S

Source: Drug Bank

Isomeric SMILES

C[C@H](CS)C(=O)N1CCC[C@H]1C(=O)O

Source: OpenEye

Canonical SMILES

C[C@H](CS)C(=O)N1CCC[C@H]

Source: Drug Bank

Average Molecular Weight

217.285

Source: Drug Bank

Monoisotopic Molecular Weight

217.077264041

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
ACE
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
ACE2
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
AGT
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
AGTR1

Drug Targets

Gene Description
ACE (source: Drug Bank)
ALB (source: Drug Bank)
ATP1A1 (source: Drug Bank)
MMP2 (source: Drug Bank)
MMP9 (source: Drug Bank)

Drug Interactions

Drug Description
captopril Increased risk of hyperkaliemia (source: Drug Bank)
captopril 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)
captopril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
captopril The ACE inhibitor increases serum levels of lithium (source: Drug Bank)
captopril Increased risk of hyperkaliemia (source: Drug Bank)
captopril Increased risk of hyperkaliemia (source: Drug Bank)
captopril Terbinafine may reduce the metabolism and clearance of Captopril. Consider alternate therapy or monitor for therapeutic/adverse effects of Captopril if Terbinafine is initiated, discontinued or dose changed. (source: Drug Bank)
captopril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
captopril Tizanidine increases the risk of hypotension with the ACE inhibitor (source: Drug Bank)
captopril Increased risk of nephrotoxicity (source: Drug Bank)
captopril The 2D6 inhibitor, Trazodone, may increase the efficacy of Captopril by decreasing Captopril metabolism and clearance. Monitor for changes in Captopril efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
captopril The 2D6 inhibitor, Trazodone, may increase the efficacy of Captopril by decreasing Captopril metabolism and clearance. Monitor for changes in Captopril efficacy if Trazodone is initiated, discontinued or dose changed. (source: Drug Bank)
captopril Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use. (source: Drug Bank)
captopril Increased risk of hyperkaliemia (source: Drug Bank)
captopril 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 captopril: 14

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ACE gene polymorphism and serum ACE activity in Iranians type II diabetic patients with macroalbuminuria. Molecular and cellular biochemistry. 2011. Felehgari Vahid, 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
Impact of renin-angiotensin system polymorphisms on renal haemodynamic responsiveness to acute angiotensin-converting enzyme inhibition in type 2 diabetes mellitus. Journal of the renin-angiotensin-aldosterone system : JRAAS. 2009. Volkan-Salanci Bilge, 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 CA VA No VIP available No VIP available
Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women. Clinical pharmacology and therapeutics. 2007. Fan X, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effects of captopril administration on pulmonary haemodynamics and tissue oxygenation during exercise in ACE gene subtypes in patients with COPD: a preliminary study. Thorax. 2003. Kanazawa H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene on response to angiotensin-converting enzyme inhibitors in patients with heart failure. Journal of cardiovascular pharmacology. 1998. O'Toole L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Angiotensin converting enzyme gene polymorphism and ACE inhibition in diabetic nephropathy. Kidney international. 1998. Jacobsen P, 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
Contribution of angiotensin I converting enzyme gene polymorphism and angiotensinogen gene polymorphism to blood pressure regulation in essential hypertension. American journal of hypertension. 1998. Mondorf U 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
Angiotensin-converting enzyme inhibitors promote nitric oxide production in coronary microvessels from failing explanted human hearts. The American journal of cardiology. 1997. Kichuk M R, 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
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
Renal hemodynamic changes induced by captopril and angiotensin-converting enzyme gene polymorphism. Nephron. 1997. Mizuiri S, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effect of deletion polymorphism of angiotensin converting enzyme gene on progression of diabetic nephropathy during inhibition of angiotensin converting enzyme: observational follow up study. BMJ (Clinical research ed.). 1996. Parving H H, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-3007-01
DrugBank:
DB01197
ChEBI:
3380
KEGG Drug:
D00251
PubChem Compound:
44093
PubChem Substance:
46506879
7847317
Drugs Product Database (DPD):
2242791
BindingDB:
21642
ChemSpider:
40130
Therapeutic Targets Database:
DAP000589
FDA Drug Label at DailyMed:
5599d8f8-efc8-4acc-a507-280b89fd1dda

Clinical Trials

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

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