Fosinopril

Identification

Summary

Fosinopril is an ACE inhibitor used to treat mild to moderate hypertension, congestive heart failure, and to slow the progression of renal disease in hypertensive diabetics.

Generic Name
Fosinopril
DrugBank Accession Number
DB00492
Background

Fosinopril is a phosphinic acid-containing ester prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly hydrolyzed to fosinoprilat, its principle active metabolite. Fosinoprilat inhibits 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). Fosinopril may be used to treat mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 563.672
Monoisotopic: 563.301189823
Chemical Formula
C30H46NO7P
Synonyms
  • Fosenopril
  • Fosinopril

Pharmacology

Indication

For treating mild to moderate hypertension, use as an adjunct in treating congestive heart failure, and may be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in management ofHeart failure••••••••••••••••••
Used in combination to manageHypertensionCombination Product in combination with: Hydrochlorothiazide (DB00999)••••••••••••••••••
Management ofHypertension••••••••••••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Following oral administration, fosinopril is rapidly and completely hydrolyzed to its principle active metabolite, fosinoprilat. Hydrolysis is thought to occur in the gastrointestinal mucosa and liver. Fosinoprilat is a competitive inhibitor of ACE, a peptidyl dipeptidase that is part 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 further sustain the effects of fosinoprilat 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. Fosinoprilat, the active metabolite of fosinopril, 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. Fosinoprilat 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
Humans
Absorption

Average absolute absorption is 36%. The primary site of absorption is the proximal small intestine (duodenum/jejunum). Food slows the rate of absorption with no effect on the extent of absorption.

Volume of distribution

Not Available

Protein binding

Fosinoprilat is ≥95% protein bound

Metabolism

Since fosinoprilat is not biotransformed after intravenous administration, fosinopril, not fosinoprilat, appears to be the precursor for the glucuronide and p-hydroxy metabolites.

Hover over products below to view reaction partners

Route of elimination

After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces.

Half-life

12 hours

Clearance
  • 26 - 39 mL/min [healthy]
Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Human overdoses of fosinopril have not been reported, but the most common manifestation of human fosinopril overdosage is likely to be hypotension. Oral doses of fosinopril at 2600 mg/kg in rats were associated with significant lethality. The most common adverse effects include dizzines, cough, fatigue, and headache.

Pathways
PathwayCategory
Fosinopril Action PathwayDrug action
Fosinopril Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirFosinopril may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbaloparatideThe risk or severity of adverse effects can be increased when Fosinopril is combined with Abaloparatide.
AcebutololFosinopril may increase the hypotensive activities of Acebutolol.
AceclofenacThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Aceclofenac is combined with Fosinopril.
AcemetacinThe risk or severity of renal failure, hyperkalemia, and hypertension can be increased when Acemetacin is combined with Fosinopril.
Food Interactions
  • Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice).
  • Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
  • Limit salt intake. Salt may attenuate the antihypertensive effect.
  • Take separate from antacids. Take at least 2 hours before or after antacids. Taking this medication with antacids can reduce absorption.Taking this medication with antacids can reduce absorption.
  • Take with or without food. The absorption is unaffected by food.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Fosinopril sodiumNW2RTH6T2N88889-14-9TVTJZMHAIQQZTL-LVCDZQEYSA-M
Active Moieties
NameKindUNIICASInChI Key
FosinoprilatprodrugS312EY6ZT895399-71-6WOIWWYDXDVSWAZ-RTWAWAEBSA-N
Product Images
International/Other Brands
Acecor (SPA (Czech Republic)) / Monopril / Staril (BMS (United Kingdom))
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
FosinoprilTablet20 mgOralSanis Health Inc2017-04-11Not applicableCanada flag
FosinoprilTablet10 mgOralSanis Health Inc2017-04-11Not applicableCanada flag
Fosinopril TabletsTablet20 mgOralRanbaxy Inc.Not applicableNot applicableCanada flag
Fosinopril TabletsTablet10 mgOralRanbaxy Inc.Not applicableNot applicableCanada flag
Fosinopril-10Tablet10 mgOralPro Doc Limitee2008-10-232021-07-27Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-fosinoprilTablet10 mgOralApotex Corporation2005-04-27Not applicableCanada flag
Apo-fosinoprilTablet20 mgOralApotex Corporation2005-04-27Not applicableCanada flag
Ava-fosinoprilTablet10 mgOralAvanstra Inc2011-11-282014-08-21Canada flag
Ava-fosinoprilTablet20 mgOralAvanstra Inc2011-11-282014-08-21Canada flag
FOSINOPRIL NaTablet10 mg/1OralApotex Corporation2005-05-182016-05-31US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Fosicomb - TablettenFosinopril sodium (20 mg) + Hydrochlorothiazide (12.5 mg)TabletOralBausch Health Ireland Limited1997-05-03Not applicableAustria flag
FOSICOMBIFosinopril (20 MG) + Hydrochlorothiazide (12.5 MG)TabletOralA. Menarini Industrie Farmaceutiche Riunite s.r.l.2014-07-08Not applicableItaly flag
FOSINOPRIL E IDROCLOROTIAZIDE DOC GENERICIFosinopril (20 MG) + Hydrochlorothiazide (12.5 MG)TabletOralDoc Generici Srl2014-07-08Not applicableItaly flag
FOSINOPRIL E IDROCLOROTIAZIDE DOC GENERICIFosinopril (20 MG) + Hydrochlorothiazide (12.5 MG)TabletOralDoc Generici Srl2014-07-08Not applicableItaly flag
FOSINOPRIL E IDROCLOROTIAZIDE DOC GENERICIFosinopril (20 MG) + Hydrochlorothiazide (12.5 MG)TabletOralDoc Generici Srl2014-07-08Not applicableItaly flag

Categories

ATC Codes
C09BA09 — Fosinopril and diureticsC09AA09 — Fosinopril
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
R43D2573WO
CAS number
98048-97-6
InChI Key
BIDNLKIUORFRQP-FLODCBCLSA-N
InChI
InChI=1S/C30H46NO7P/c1-4-28(33)37-30(22(2)3)38-39(36,18-12-11-15-23-13-7-5-8-14-23)21-27(32)31-20-25(19-26(31)29(34)35)24-16-9-6-10-17-24/h5,7-8,13-14,22,24-26,30H,4,6,9-12,15-21H2,1-3H3,(H,34,35)/t25-,26+,30+,39+/m1/s1
IUPAC Name
(2S,4S)-4-cyclohexyl-1-(2-{[(1S)-2-methyl-1-(propanoyloxy)propoxy](4-phenylbutyl)phosphoryl}acetyl)pyrrolidine-2-carboxylic acid
SMILES
CCC(=O)O[C@@H](OP(=O)(CCCCC1=CC=CC=C1)CC(=O)N1C[C@@H](C[C@H]1C(O)=O)C1CCCCC1)C(C)C

References

Synthesis Reference

Sandra Gallego Pato, Antonio Palomo Coll, Francisco Palomo Nicolau, "Preparation of crystalline polymorphs of fosinopril sodium." U.S. Patent US20050010054, issued January 13, 2005.

US20050010054
General References
  1. David D, Jallad N, Germino FW, Willett MS, de Silva J, Weidner SM, Mills DJ: A Comparison of the Cough Profile of Fosinopril and Enalapril in Hypertensive Patients with a History of ACE Inhibitor-Associated Cough. Am J Ther. 1995 Oct;2(10):806-813. [Article]
  2. Sharma S, Deitchman D, Eni JS, Gelperin K, Ilgenfritz JP, Blumenthal M: The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group. Am J Ther. 1999 Jul;6(4):181-9. [Article]
  3. DailyMed: Aurobindo Fosinopril sodium and Hydrochlorothiazide oral tablets [Link]
  4. DailyMEd: Aurobindo Fosinopril sodium oral tablets [Link]
Human Metabolome Database
HMDB0014635
KEGG Drug
D07992
KEGG Compound
C07016
PubChem Compound
55891
PubChem Substance
46506495
ChemSpider
23089342
RxNav
50166
ChEBI
5163
ChEMBL
CHEMBL3039598
ZINC
ZINC000003920355
Therapeutic Targets Database
DAP000582
PharmGKB
PA449710
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Fosinopril
FDA label
Download (206 KB)

Clinical Trials

Clinical Trials

Pharmacoeconomics

Manufacturers
  • Apotex inc etobicoke site
  • Invagen pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Watson laboratories inc florida
  • Bristol myers squibb co pharmaceutical research institute
Packagers
  • Apotex Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Blu Pharmaceuticals LLC
  • Bristol-Myers Squibb Co.
  • Cobalt Pharmaceuticals Inc.
  • Deca Pharmaceuticals LLC
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Eon Labs
  • Glenmark Generics Ltd.
  • InvaGen Pharmaceuticals Inc.
  • Ivax Pharmaceuticals
  • Kaiser Foundation Hospital
  • Murfreesboro Pharmaceutical Nursing Supply
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Princeton Pharmaceutical Products Inc.
  • Ranbaxy Laboratories
  • Resource Optimization and Innovation LLC
  • Teva Pharmaceutical Industries Ltd.
  • Va Cmop Dallas
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
TabletOral
TabletOral
TabletOral5 MG
Tablet, film coated
TabletOral10 mg/1
TabletOral20 mg/1
TabletOral40 mg/1
TabletOral10 mg
TabletOral20 mg
Prices
Unit descriptionCostUnit
Monopril HCT 10-12.5 mg tablet1.71USD tablet
Monopril 10 mg tablet1.68USD tablet
Monopril 40 mg tablet1.67USD tablet
Monopril 20 mg tablet1.62USD tablet
Fosinopril Sodium-HCTZ 10-12.5 mg tablet1.61USD tablet
Fosinopril Sodium-HCTZ 20-12.5 mg tablet1.61USD tablet
Fosinopril sodium 20 mg tablet1.25USD tablet
Fosinopril sodium 40 mg tablet1.25USD tablet
Fosinopril sodium 10 mg tablet1.21USD tablet
Monopril 20 mg Tablet1.1USD tablet
Monopril 10 mg Tablet0.91USD tablet
Apo-Fosinopril 20 mg Tablet0.61USD tablet
Fosinopril 20 mg Tablet0.61USD tablet
Jamp-Fosinopril 20 mg Tablet0.61USD tablet
Mylan-Fosinopril 20 mg Tablet0.61USD tablet
Novo-Fosinopril 20 mg Tablet0.61USD tablet
Ran-Fosinopril 20 mg Tablet0.61USD tablet
Apo-Fosinopril 10 mg Tablet0.51USD tablet
Fosinopril 10 mg Tablet0.51USD tablet
Jamp-Fosinopril 10 mg Tablet0.51USD tablet
Mylan-Fosinopril 10 mg Tablet0.51USD tablet
Novo-Fosinopril 10 mg Tablet0.51USD tablet
Ran-Fosinopril 10 mg Tablet0.51USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5006344No1991-04-092010-01-10US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)149-153 °CNot Available
water solubilityInsolubleNot Available
logP6.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00101 mg/mLALOGPS
logP4.71ALOGPS
logP5.62Chemaxon
logS-5.8ALOGPS
pKa (Strongest Acidic)3.87Chemaxon
pKa (Strongest Basic)-4.4Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area110.21 Å2Chemaxon
Rotatable Bond Count15Chemaxon
Refractivity149.12 m3·mol-1Chemaxon
Polarizability62.27 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9532
Blood Brain Barrier-0.667
Caco-2 permeable-0.6561
P-glycoprotein substrateSubstrate0.6165
P-glycoprotein inhibitor IInhibitor0.7161
P-glycoprotein inhibitor IINon-inhibitor0.6774
Renal organic cation transporterNon-inhibitor0.812
CYP450 2C9 substrateNon-substrate0.7028
CYP450 2D6 substrateNon-substrate0.8128
CYP450 3A4 substrateSubstrate0.6729
CYP450 1A2 substrateNon-inhibitor0.8913
CYP450 2C9 inhibitorNon-inhibitor0.7438
CYP450 2D6 inhibitorNon-inhibitor0.9004
CYP450 2C19 inhibitorNon-inhibitor0.5725
CYP450 3A4 inhibitorNon-inhibitor0.7303
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6376
Ames testNon AMES toxic0.7141
CarcinogenicityNon-carcinogens0.8025
BiodegradationNot ready biodegradable0.8102
Rat acute toxicity2.8211 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9534
hERG inhibition (predictor II)Non-inhibitor0.5918
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 MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-01ox-1122930000-054ad679dd586ecccc01
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0api-1080090000-5e727b7d5271cfa03388
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0083-4495700000-bcd801b2224ec15df9bc
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-1297500000-92bdce628563728c9c5c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00pj-2962210000-962b93e42212de90ab4b
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9001110000-31bba46aa5a61cdf8112
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
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. [Article]
  2. Ondetti MA: Structural relationships of angiotensin converting-enzyme inhibitors to pharmacologic activity. Circulation. 1988 Jun;77(6 Pt 2):I74-8. [Article]
  3. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. [Article]
  4. Sharma S, Deitchman D, Eni JS, Gelperin K, Ilgenfritz JP, Blumenthal M: The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group. Am J Ther. 1999 Jul;6(4):181-9. [Article]

Transporters

Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48