Identification

Name
Ramipril
Accession Number
DB00178  (APRD00009)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • (2S-(1(R*(r*)),2alpha,3abeta,6abeta))-1-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydrocyclopenta(b)pyrrole-2-carboxylic acid
  • Altace (tn)
  • Ramipril
  • Ramiprilum
  • Tritace
External IDs
C09AA05 / HOE 498
Active Moieties
NameKindUNIICASInChI Key
Ramiprilatprodrug6N5U4QFC3G87269-97-4KEDYTOTWMPBSLG-HILJTLORSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act RamiprilCapsule2.5 mgOralActavis Pharma Company2007-10-02Not applicableCanada
Act RamiprilCapsule10 mgOralActavis Pharma Company2007-10-02Not applicableCanada
Act RamiprilCapsule1.25 mgOralActavis Pharma Company2007-10-02Not applicableCanada
Act RamiprilCapsule5 mgOralActavis Pharma Company2007-10-02Not applicableCanada
AltaceTablet1.25 mg/1OralKing Pharmaceuticals, Inc.2007-02-272008-10-08Us
AltaceCapsule2.5 mg/1OralPhysicians Total Care, Inc.2002-08-122012-06-30Us
AltaceTablet5 mgOralValeant Canada Lp Valeant Canada S.E.C.Not applicableNot applicableCanada
AltaceCapsule2.5 mgOralValeant Canada Lp Valeant Canada S.E.C.1997-04-21Not applicableCanada
AltaceCapsule10 mg/1OralPfizer Laboratories Div Pfizer Inc.1991-01-28Not applicableUs
AltaceCapsule1.25 mg/1OralPfizer Laboratories Div Pfizer Inc.1991-01-28Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ach-ramiprilCapsule15 mgOralAccord Healthcare LimitedNot applicableNot applicableCanada
Ach-ramiprilCapsule2.5 mgOralAccord Healthcare LimitedNot applicableNot applicableCanada
Ach-ramiprilCapsule10 mgOralAccord Healthcare LimitedNot applicableNot applicableCanada
Ach-ramiprilCapsule1.25 mgOralAccord Healthcare LimitedNot applicableNot applicableCanada
Ach-ramiprilCapsule5 mgOralAccord Healthcare LimitedNot applicableNot applicableCanada
Apo-ramiprilCapsule15 mgOralApotex Corporation2009-05-01Not applicableCanada
Apo-ramiprilCapsule5 mgOralApotex Corporation2006-12-12Not applicableCanada
Apo-ramiprilCapsule2.5 mgOralApotex Corporation2006-12-12Not applicableCanada
Apo-ramiprilCapsule10 mgOralApotex Corporation2006-12-12Not applicableCanada
Apo-ramiprilCapsule1.25 mgOralApotex Corporation2006-12-12Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Altace HctRamipril (5.0 mg) + Hydrochlorothiazide (25.0 mg)TabletOralValeant Canada Lp Valeant Canada S.E.C.2006-11-16Not applicableCanada
Altace HctRamipril (2.5 mg) + Hydrochlorothiazide (12.5 mg)TabletOralValeant Canada Lp Valeant Canada S.E.C.2006-11-16Not applicableCanada
Altace HctRamipril (10.0 mg) + Hydrochlorothiazide (12.5 mg)TabletOralValeant Canada Lp Valeant Canada S.E.C.2006-11-16Not applicableCanada
Altace HctRamipril (10.0 mg) + Hydrochlorothiazide (25.0 mg)TabletOralValeant Canada Lp Valeant Canada S.E.C.2006-11-16Not applicableCanada
Altace HctRamipril (5 mg) + Hydrochlorothiazide (12.5 mg)TabletOralValeant Canada Lp Valeant Canada S.E.C.2006-11-16Not applicableCanada
Altace Plus Felodipine 2.5mg + 2.5mgRamipril (2.5 mg) + Felodipine (2.5 mg)TabletOralSanofi Aventis2006-06-272012-10-10Canada
Altace Plus Felodipine 5mg + 5mgRamipril (5 mg) + Felodipine (5 mg)TabletOralSanofi Aventis2006-06-272012-10-15Canada
Apo-ramipril/hctzRamipril (10 mg) + Hydrochlorothiazide (25 mg)TabletOralApotex CorporationNot applicableNot applicableCanada
Apo-ramipril/hctzRamipril (5 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex CorporationNot applicableNot applicableCanada
Apo-ramipril/hctzRamipril (2.5 mg) + Hydrochlorothiazide (12.5 mg)TabletOralApotex CorporationNot applicableNot applicableCanada
International/Other Brands
Acovil (Sanofi-Aventis (Spain)) / Carasel (Almirall (Spain)) / Cardace (Sanofi-Aventis (Finland), Aventis (India), Aventis (Indonesia)) / Delix (Aventis (Germany, Turkey), ) / Hypren (AstraZeneca (Austria)) / Lostapres (Temis (Argentina)) / Pramace (Astra (Ireland), AstraZeneca (Sweden)) / Quark (Polifarma (Italy)) / Triatec (Sanofi-Aventis (Brazil, Chili, Denmark, France, Greece, Indonesia, Italy,Norway, Portugal, Sweden, Switzerland)) / Tritace (Sanofi-Aventis (Argentina, Australia, Austria, Belgium, Czech Republic, Hong Kong, Hungary, Ireland, Israel, Malaysia, Mexico, Netherlands, Poland, Singapor, Thailand, United Kingdom), Aventis (New Zealand, Philippines, South Africa)) / Vesdil (AstraZeneca (Germany), Promed (Germany))
Categories
UNII
L35JN3I7SJ
CAS number
87333-19-5
Weight
Average: 416.5106
Monoisotopic: 416.231122144
Chemical Formula
C23H32N2O5
InChI Key
HDACQVRGBOVJII-JBDAPHQKSA-N
InChI
InChI=1S/C23H32N2O5/c1-3-30-23(29)18(13-12-16-8-5-4-6-9-16)24-15(2)21(26)25-19-11-7-10-17(19)14-20(25)22(27)28/h4-6,8-9,15,17-20,24H,3,7,10-14H2,1-2H3,(H,27,28)/t15-,17-,18-,19-,20-/m0/s1
IUPAC Name
(2S,3aS,6aS)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]-octahydrocyclopenta[b]pyrrole-2-carboxylic acid
SMILES
[H][C@@]12CCC[C@]1([H])N([C@@H](C2)C(O)=O)C(=O)[C@H](C)N[C@@H](CCC1=CC=CC=C1)C(=O)OCC

Pharmacology

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.

Associated Conditions
Pharmacodynamics

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.

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.

TargetActionsOrganism
AAngiotensin-converting enzyme
inhibitor
Human
UB1 bradykinin receptorNot AvailableHuman
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.

Volume of distribution
Not Available
Protein binding

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

Metabolism

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.

Route of elimination
Not Available
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.

Clearance
Not Available
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. LD50 = 10933 mg/kg (orally in mice).

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Ramipril Action PathwayDrug action
Ramipril Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Angiotensin-converting enzyme---(A;A) / (G;G)A Allele, homozygote / G Allele, homozygoteEffect Directly StudiedPatients with this genotype have a shorter time to lowering of blood pressure with ramiprilDetails

Interactions

Drug Interactions
DrugInteraction
AcebutololThe risk or severity of adverse effects can be increased when Ramipril is combined with Acebutolol.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Ramipril.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Ramipril.
Acetylsalicylic acidThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acetylsalicylic acid is combined with Ramipril.
AgmatineThe risk or severity of hyperkalemia can be increased when Ramipril is combined with Agmatine.
Agrostis gigantea pollenThe risk or severity of adverse effects can be increased when Ramipril is combined with Agrostis gigantea pollen.
Agrostis stolonifera pollenThe risk or severity of adverse effects can be increased when Ramipril is combined with Agrostis stolonifera pollen.
AlclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Alclofenac is combined with Ramipril.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Ramipril.
AlfuzosinAlfuzosin may increase the hypotensive activities of Ramipril.
Food Interactions
  • Alcohol may increase the vasodilatory effects of ramipril.
  • 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.
  • Ramipril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.
  • Take without regard to meals.

References

Synthesis Reference

Edward Wilson, Martin Beasley, "Stabilized ramipril compositions and methods of making." U.S. Patent US20060134213, issued June 22, 2006.

US20060134213
General References
  1. Cacciapuoti F, Capasso A, Mirra G, De Nicola A, Minicucci F, Gentile S: Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine. Int J Cardiol. 1998 Jan 31;63(2):175-8. [PubMed:9510492]
  2. Kleinert S: HOPE for cardiovascular disease prevention with ACE-inhibitor ramipril. Heart Outcomes Prevention Evaluation. Lancet. 1999 Sep 4;354(9181):841. [PubMed:10485736]
External Links
Human Metabolome Database
HMDB0014324
KEGG Drug
D00421
PubChem Compound
5362129
PubChem Substance
46506390
ChemSpider
4514937
BindingDB
50084681
ChEBI
8774
ChEMBL
CHEMBL1168
Therapeutic Targets Database
DAP000581
PharmGKB
PA451223
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ramipril
ATC Codes
C10BX04 — Simvastatin, acetylsalicylic acid and ramiprilC09AA05 — RamiprilC10BX06 — Atorvastatin, acetylsalicylic acid and ramiprilC09BA05 — Ramipril and diureticsC09BB07 — Ramipril and amlodipineC09BB05 — Ramipril and felodipine
AHFS Codes
  • 24:32.04 — Angiotensin-converting Enzyme Inhibitors
MSDS
Download (53.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers6
1CompletedTreatmentHealthy Volunteers7
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1RecruitingBasic ScienceDiabetes Mellitus (DM) / Healthy Volunteers1
1WithdrawnTreatmentHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
2CompletedBasic ScienceHigh Blood Pressure (Hypertension)1
2CompletedTreatmentAtherosclerosis / Coronary Heart Disease (CHD) / Vasculitis1
2CompletedTreatmentChronic Kidney Disease (CKD)1
2CompletedTreatmentComplication of Hemodialysis / End Stage Renal Failure on Dialysis1
2CompletedTreatmentHeart Failure, Unspecified1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / Inflammatory Reaction1
2CompletedTreatmentLupus / Systemic Lupus Erythematosus (SLE)1
2CompletedTreatmentMigraine With Hypertension1
2Not Yet RecruitingTreatmentMyocardial Infarction1
2RecruitingSupportive CareChemoradiation / Cognitive Decline / Glioblastomas / Radiotherapy; Complications1
2RecruitingTreatmentBMI >30 kg/m2 / Diabetes, Diabetes Mellitus Type 1 / Type 2 Diabetes Mellitus1
2RecruitingTreatmentHigh Blood Pressure (Hypertension)1
2TerminatedNot AvailableHigh Blood Pressure (Hypertension)1
2TerminatedPreventionElevated LDL Cholesterol2
2TerminatedTreatmentHigh Blood Pressure (Hypertension) / Unspecified Adult Solid Tumor, Protocol Specific1
2TerminatedTreatmentNon-diabetic Nephropathy1
2, 3CompletedPreventionNonvalvular Atrial Fibrillation1
2, 3CompletedTreatmentDiabetes Mellitus (DM)1
2, 3CompletedTreatmentRheumatoid Arthritis1
3Active Not RecruitingTreatmentRenal Insufficiency,Chronic1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Impaired Glucose Tolerance (IGT) / Isolated Impaired Fasting Glucose1
3CompletedPreventionCardiovascular Disease (CVD) / Glucose Metabolism Disorders / Impaired Glucose Tolerance (IGT)1
3CompletedPreventionMyocardial Infarction1
3CompletedTreatmentAcquired Kidney Disease / Children / Chronic Renal Failure (CRF) / Congenital Kidney Disease / High Blood Pressure (Hypertension)1
3CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
3CompletedTreatmentBiopsy-confirmed IgA Nephropathy / Normal Blood Pressure / Proteinuria Less Than 0.5 g Per Day / Serum Creatinine Below 120 Umol/l1
3CompletedTreatmentDiabetes Mellitus (DM) / Impaired Glucose Tolerance (IGT)1
3CompletedTreatmentDiabetes Mellitus (DM) / Microalbuminuria1
3CompletedTreatmentDiabetic Nephropathies1
3CompletedTreatmentGlomerulonephritis1
3CompletedTreatmentHigh Blood Pressure (Hypertension)5
3CompletedTreatmentMyocardial Ischemia1
3CompletedTreatmentTransplantation, Kidney1
3Not Yet RecruitingTreatmentArrhythmogenic Right Ventricular Dysplasia1
3RecruitingPreventionCancer, Breast / Cardiotoxicity1
3RecruitingTreatmentAcute Myocardial Infarction (AMI)1
3TerminatedHealth Services ResearchEndothelial Dysfunction / Oxidative Stress1
3TerminatedPreventionDiabetes, Diabetes Mellitus Type 11
3TerminatedTreatmentAlbuminuria / High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
3TerminatedTreatmentAtrial Flutter / Nonvalvular Atrial Fibrillation1
3TerminatedTreatmentHigh Blood Pressure (Hypertension)1
3Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Microalbuminuria / Type 2 Diabetes Mellitus1
4Active Not RecruitingTreatmentAcute Heart Failure (AHF)1
4Active Not RecruitingTreatmentDiabetes Mellitus (DM) / Hypertensive Disease1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedPreventionAdverse Effects / Coronary Artery Atherosclerosis / Insulin resistance syndrome1
4CompletedPreventionAlzheimer's Disease (AD) / High Blood Pressure (Hypertension)1
4CompletedPreventionCardiovascular Disease (CVD)1
4CompletedPreventionDiabetes Mellitus (DM) / Proteinuria / Renin Angiotensin System1
4CompletedPreventionHigh Blood Pressure (Hypertension)1
4CompletedTreatmentAlbuminuria1
4CompletedTreatmentAngiotensin Converting Enzyme / Angiotensin Receptor Blockers / Cardiopulmonary Bypass / Coronary Artery Disease / Fibrinolysis / Inflammatory Reaction1
4CompletedTreatmentAtherosclerosis1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentChronic Kidney Disease (CKD) / Diabetic Nephropathies / Proteinuria2
4CompletedTreatmentHeart Failure, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)10
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Hypertension,Essential1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Induction of intra-operative hypotension1
4CompletedTreatmentHypertension,Essential1
4CompletedTreatmentIntermittent Claudicants1
4CompletedTreatmentMicrovascular Angina1
4CompletedTreatmentPeripheral Arterial Disease (PAD)2
4CompletedTreatmentTransplant, Kidney1
4RecruitingTreatmentAngiotensin-Converting Enzyme Inhibitors / Transcatheter Aortic Valve Replacemen1
4RecruitingTreatmentCoronary Artery Dissection, Spontaneous1
4RecruitingTreatmentHigh Blood Pressure (Hypertension) / High Blood Pressure Variability1
4RecruitingTreatmentHypertension Resistant To Conventional Therapy1
4RecruitingTreatmentKidney Transplant; Complications / New Onset Diabetes After Transplant1
4RecruitingTreatmentPeripheral Arterial Disease (PAD)1
4TerminatedPreventionMetabolic Syndromes1
4TerminatedTreatmentHypertension With Metabolic Syndrome1
4Unknown StatusPreventionBecker's Muscular Dystrophy (BMD) / Duchenne's Muscular Dystrophy (DMD)1
4Unknown StatusPreventionDiabetic Nephropathies1
4Unknown StatusTreatmentAcute Coronary Syndromes (ACS) / Coronary Heart Disease (CHD) / Myocardial Infarction1
4Unknown StatusTreatmentAntihypertensive Drugs / Diastolic Function / Hypertensive Heart Disease / Left Atrial Volume / Renin Angiotensin System1
4Unknown StatusTreatmentDiabetic Nephropathies / Type 2 Diabetes Mellitus / Vascular Diseases1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4Unknown StatusTreatmentHypertension,Essential1
4WithdrawnTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedBasic ScienceAgeing / Left Ventricular Function Diastolic Dysfunction / Left Ventricular Function Systolic Dysfunction1
Not AvailableCompletedBasic ScienceMetabolic Syndromes1
Not AvailableCompletedPreventionCardiac Allograft Vasculopathy1
Not AvailableCompletedPreventionCardiovascular Disease (CVD)1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)2
Not AvailableRecruitingNot AvailableAlport Syndrome / Familial Benign Hematuria / Hereditary Kidney Disease / Pediatric Kidney Disease / Thin Basement Membrane Disease1
Not AvailableRecruitingNot AvailableChronic Kidney Disease (CKD)1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableTerminatedPreventionMetabolic Syndromes1
Not AvailableUnknown StatusTreatmentAsthenozoospermia / Male Infertility / Oligozoospermia / Teratospermia1

Pharmacoeconomics

Manufacturers
  • King pharmaceuticals inc
  • Actavis elizabeth llc
  • Apotex inc
  • Cipla ltd
  • Dr reddys laboratories ltd
  • Invagen pharmaceuticals inc
  • Lupin ltd
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Sandoz inc
  • Teva pharmaceuticals usa
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
  • King Pharmaceuticals, Inc.
Packagers
  • Amerisource Health Services Corp.
  • Apotex Inc.
  • Arrow Pharm Malta Ltd.
  • A-S Medication Solutions LLC
  • Blu Pharmaceuticals LLC
  • Bryant Ranch Prepack
  • Camber Pharmaceuticals Inc.
  • Cardinal Health
  • Cipla Ltd.
  • Cobalt Pharmaceuticals Inc.
  • DAVA Pharmaceuticals
  • Dispensing Solutions
  • Doctor Reddys Laboratories Ltd.
  • Heartland Repack Services LLC
  • Hoechst Marion Roussel Canada Inc.
  • InvaGen Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • King Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Lupin Pharmaceuticals Inc.
  • Mckesson Corp.
  • Monarch Pharmacy
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Roxane Labs
  • Sandoz
  • Sanofi-Aventis Inc.
  • Southwood Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral1.25 mg/1
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral5 mg/1
CapsuleOral15 mg
CapsuleOral15.0 mg
CapsuleOral5.0 mg
CapsuleOral1.25 mg
CapsuleOral10 mg
CapsuleOral2.5 mg
CapsuleOral5 mg
TabletOral
CapsuleOral1.25 mg/1
CapsuleOral10 mg/301
CapsuleOral10 mg/1
CapsuleOral2.5 mg/1
CapsuleOral5 mg/1
Capsule, gelatin coatedOral1.25 mg/1
Capsule, gelatin coatedOral10 mg/1
Capsule, gelatin coatedOral2.5 mg/1
Capsule, gelatin coatedOral5 mg/1
CapsuleOral10.0 mg
TabletOral1.25 mg
TabletOral10 mg
TabletOral2.5 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Altace 10 mg capsule2.87USD capsule
Altace 2.5 mg capsule2.54USD capsule
Altace 5 mg capsule2.53USD capsule
Altace 10 mg tablet2.37USD tablet
Altace 1.25 mg capsule2.2USD capsule
Ramipril 10 mg capsule2.19USD capsule
Altace 5 mg tablet2.02USD tablet
Altace 2.5 mg tablet1.93USD tablet
Ramipril 5 mg capsule1.87USD capsule
Ramipril 2.5 mg capsule1.78USD capsule
Altace 1.25 mg tablet1.63USD tablet
Ramipril 1.25 mg capsule1.59USD capsule
Altace 10 mg Tablet1.14USD tablet
Altace 2.5 mg Tablet0.9USD tablet
Altace 5 mg Tablet0.9USD tablet
Altace 1.25 mg Tablet0.78USD tablet
Apo-Ramipril 10 mg Tablet0.64USD tablet
Co Ramipril 10 mg Tablet0.64USD tablet
Jamp-Ramipril 10 mg Tablet0.64USD tablet
Mylan-Ramipril 10 mg Tablet0.64USD tablet
Novo-Ramipril 10 mg Tablet0.64USD tablet
Pms-Ramipril 10 mg Tablet0.64USD tablet
Ramipril 10 mg Tablet0.64USD tablet
Ran-Ramipril 10 mg Tablet0.64USD tablet
Ratio-Ramipril 10 mg Tablet0.64USD tablet
Sandoz Ramipril 10 mg Tablet0.64USD tablet
Apo-Ramipril 2.5 mg Tablet0.5USD tablet
Apo-Ramipril 5 mg Tablet0.5USD tablet
Co Ramipril 2.5 mg Tablet0.5USD tablet
Co Ramipril 5 mg Tablet0.5USD tablet
Jamp-Ramipril 2.5 mg Tablet0.5USD tablet
Jamp-Ramipril 5 mg Tablet0.5USD tablet
Mylan-Ramipril 2.5 mg Tablet0.5USD tablet
Mylan-Ramipril 5 mg Tablet0.5USD tablet
Novo-Ramipril 2.5 mg Tablet0.5USD tablet
Novo-Ramipril 5 mg Tablet0.5USD tablet
Pms-Ramipril 2.5 mg Tablet0.5USD tablet
Pms-Ramipril 5 mg Tablet0.5USD tablet
Ramipril 2.5 mg Tablet0.5USD tablet
Ramipril 5 mg Tablet0.5USD tablet
Ran-Ramipril 2.5 mg Tablet0.5USD tablet
Ran-Ramipril 5 mg Tablet0.5USD tablet
Ratio-Ramipril 2.5 mg Tablet0.5USD tablet
Ratio-Ramipril 5 mg Tablet0.5USD tablet
Sandoz Ramipril 2.5 mg Tablet0.5USD tablet
Sandoz Ramipril 5 mg Tablet0.5USD tablet
Apo-Ramipril 1.25 mg Tablet0.44USD tablet
Co Ramipril 1.25 mg Tablet0.44USD tablet
Jamp-Ramipril 1.25 mg Tablet0.44USD tablet
Mylan-Ramipril 1.25 mg Tablet0.44USD tablet
Pms-Ramipril 1.25 mg Tablet0.44USD tablet
Ramipril 1.25 mg Tablet0.44USD tablet
Ran-Ramipril 1.25 mg Tablet0.44USD tablet
Ratio-Ramipril 1.25 mg Tablet0.44USD tablet
Sandoz Ramipril 1.25 mg Tablet0.44USD tablet
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Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5403856No1995-04-042012-04-04Us
CA2382387No2005-06-212020-08-25Canada
CA1338344No1996-05-212013-05-21Canada
US7368469No2008-05-062020-08-30Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)109 °CPhysProp
water solubility3.5mg/LNot Available
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.039 mg/mLALOGPS
logP0.92ALOGPS
logP1.47ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)3.75ChemAxon
pKa (Strongest Basic)5.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area95.94 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity111.19 m3·mol-1ChemAxon
Polarizability44.78 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9159
Blood Brain Barrier-0.8726
Caco-2 permeable-0.8491
P-glycoprotein substrateSubstrate0.7263
P-glycoprotein inhibitor INon-inhibitor0.7002
P-glycoprotein inhibitor IIInhibitor0.6295
Renal organic cation transporterNon-inhibitor0.8869
CYP450 2C9 substrateNon-substrate0.8541
CYP450 2D6 substrateNon-substrate0.8969
CYP450 3A4 substrateNon-substrate0.5082
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9304
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5691
Ames testNon AMES toxic0.9108
CarcinogenicityNon-carcinogens0.9267
BiodegradationNot ready biodegradable0.8903
Rat acute toxicity1.6732 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.98
hERG inhibition (predictor II)Non-inhibitor0.7901
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00lr-3930000000-ea57777ac9a14b1e9083

Taxonomy

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
Alpha amino acid esters / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Pyrrolidine carboxylic acids / N-acylpyrrolidines / Fatty acid esters / Aralkylamines / Dicarboxylic acids and derivatives / Benzene and substituted derivatives / Tertiary carboxylic acid amides
show 9 more
Substituents
Alpha-dipeptide / Alpha-amino acid ester / N-acyl-l-alpha-amino acid / N-acyl-alpha-amino acid / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / Alpha-amino acid or derivatives / Pyrrolidine carboxylic acid / Pyrrolidine carboxylic acid or derivatives / N-acylpyrrolidine
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
dicarboxylic acid monoester, ethyl ester, azabicycloalkane, dipeptide, cyclopentapyrrole (CHEBI:8774)

Targets

Kind
Protein
Organism
Human
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Levitt DG, Schoemaker RC: Human physiologically based pharmacokinetic model for ACE inhibitors: ramipril and ramiprilat. BMC Clin Pharmacol. 2006 Jan 6;6:1. [PubMed:16398929]
  3. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. [PubMed:11030016]
  4. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [PubMed:11929321]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Peptide binding
Specific Function
This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
Gene Name
BDKRB1
Uniprot ID
P46663
Uniprot Name
B1 bradykinin receptor
Molecular Weight
40494.29 Da
References
  1. Ignjatovic T, Tan F, Brovkovych V, Skidgel RA, Erdos EG: Novel mode of action of angiotensin I converting enzyme inhibitors: direct activation of bradykinin B1 receptor. J Biol Chem. 2002 May 10;277(19):16847-52. Epub 2002 Mar 5. [PubMed:11880373]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Shah GB, Sharma S, Mehta AA, Goyal RK: Oculohypotensive effect of angiotensin-converting enzyme inhibitors in acute and chronic models of glaucoma. J Cardiovasc Pharmacol. 2000 Aug;36(2):169-75. [PubMed:10942157]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [PubMed:18713951]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Knutter I, Wollesky C, Kottra G, Hahn MG, Fischer W, Zebisch K, Neubert RH, Daniel H, Brandsch M: Transport of angiotensin-converting enzyme inhibitors by H+/peptide transporters revisited. J Pharmacol Exp Ther. 2008 Nov;327(2):432-41. doi: 10.1124/jpet.108.143339. Epub 2008 Aug 19. [PubMed:18713951]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 07:14