Banner
Identification
Name Benazepril
Accession Number DB00542 (APRD00063)
Type small molecule
Groups approved
Description

Benazepril, brand name Lotensin, is a medication used to treat high blood pressure (hypertension), congestive heart failure, and chronic renal failure. Upon cleavage of its ester group by the liver, benazepril is converted into its active form benazeprilat, a non-sulfhydryl angiotensin-converting enzyme (ACE) inhibitor.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Benazepril HCl
  • Benazepril Hydrochloride
  • Benazeprilum [Latin]
Brand names
  • Briem (Pierre Fabre (France))
  • Cibacen (Novartis (Belgium, Philippines, Switzerland, Turkey), Meda (Denmark, Germany, Greece, Ireland, Italy, Netherlands, Spain))
  • Cibacene (Meda (France))
  • Lotensin (Novartis Pharmaceuticals)
Brand name mixtures
  • Lotensin HCT (benazepril hydrochloride + hydrochlorothiazide)
  • Lotrel (benazepril hydrochloride + amlodipine besylate)
Categories
  • Antihypertensive Agents
  • Angiotensin-converting Enzyme Inhibitors
CAS number 86541-75-5
Weight Average: 424.4895
Monoisotopic: 424.199822016
Chemical Formula C24H28N2O5
InChI Key InChIKey=XPCFTKFZXHTYIP-PMACEKPBSA-N
InChI
InChI=1S/C24H28N2O5/c1-2-31-24(30)20(14-12-17-8-4-3-5-9-17)25-19-15-13-18-10-6-7-11-21(18)26(23(19)29)16-22(27)28/h3-11,19-20,25H,2,12-16H2,1H3,(H,27,28)/t19-,20-/m0/s1
Plain Text
IUPAC Name
2-[(3S)-3-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl]acetic acid
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@H]1CCC2=C(C=CC=C2)N(CC(O)=O)C1=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylpropylamines
  • Lactams
  • Benzazepines
Substructures
  • Carboxylic Acids and Derivatives
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
  • Lactams
  • Benzazepines
  • Anilines
Pharmacology
Indication For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.
Pharmacodynamics Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by estarases to its active Benazeprilat, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Benazepril and Benazeprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Mechanism of action Benazeprilat, the active metabolite of Benazepril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Benazeprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
Absorption Peak in plasma within 0.5-1.0 hours. The extent of absorption is at least 37% as determined by urinary recovery and is not significantly influenced by the presence of food in the GI tract.
Volume of distribution Not Available
Protein binding benazepril, 97%; benazeprilat, 95%
Metabolism

Cleavage of the ester group (primarily in the liver) converts benazepril to its active metabolite, benazeprilat. Benazepril and benazeprilat may be conjugated to glucuronic acid prior to urinary excretion.

Route of elimination Benazepril and benazeprilat are cleared predominantly by renal excretion in healthy subjects with normal renal function. Nonrenal (i.e., biliary) excretion accounts for approximately 11%-12% of benazeprilat excretion in healthy subjects.
Half life 10-11 hours
Clearance
  • 0.35 L/hr/kg [pediatric hypertensive patients receiving multiple daily doses of Benazepril hydrochloride 0.1 – 0.5 mg/kg]
  • 0.13 L/hr/kg [healthy adults receiving a single dose of 10 mg]
Toxicity Most likely symptom of overdosage is severe hypotension. Most common adverse effects include headache, dizziness, fatigue, somnolence, postural dizziness, nausea, and cough.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00145 Benazepril Pathway SMP00145
Pharmacoeconomics
Manufacturers
  • Apotex inc etobicoke site
  • Aurobindo pharma ltd
  • Biokey inc
  • Genpharm inc
  • Huahai us inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc florida
  • Zydus pharmaceuticals usa inc
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
Form Route Strength
Tablet, film coated Oral 10 mg
Tablet, film coated Oral 20 mg
Tablet, film coated Oral 40 mg
Tablet, film coated Oral 5 mg
Prices
Unit description Cost Unit
Lotensin 20 mg tablet 2.08 USD tablet
Lotensin 10 mg tablet 2.0 USD tablet
Lotensin 40 mg tablet 2.0 USD tablet
Lotensin 5 mg tablet 2.0 USD tablet
Lotensin HCT 20-12.5 mg tablet 1.97 USD tablet
Lotensin HCT 10-12.5 mg tablet 1.95 USD tablet
Lotensin HCT 20-25 mg tablet 1.94 USD tablet
Lotensin hct 10-12.5 tablet 1.9 USD tablet
Lotensin hct 20-12.5 tablet 1.9 USD tablet
Lotensin hct 20-25 tablet 1.9 USD tablet
Lotensin hct 5-6.25 tablet 1.9 USD tablet
Lotensin HCT 5-6.25 mg tablet 1.31 USD tablet
Lotensin 20 mg Tablet 1.14 USD tablet
Benazepril hcl 10 mg tablet 1.07 USD tablet
Benazepril hcl 20 mg tablet 1.07 USD tablet
Benazepril hcl 40 mg tablet 1.07 USD tablet
Benazepril hcl 5 mg tablet 1.07 USD tablet
Lotensin 10 mg Tablet 0.99 USD tablet
Lotensin 5 mg Tablet 0.84 USD tablet
Apo-Benazepril 20 mg Tablet 0.79 USD tablet
Apo-Benazepril 10 mg Tablet 0.69 USD tablet
Apo-Benazepril 5 mg Tablet 0.58 USD tablet
Patents Not Available
Properties
State solid
Melting point 148-149 oC
Experimental Properties
Property Value Source
water solubility 2.229 mg/L PhysProp
logP 3.3 PhysProp
Predicted Properties
Property Value Source
water solubility 1.05e-02 g/l ALOGPS
logP 1.14 ALOGPS
logP 1.48 ChemAxon Molconvert
logS -4.61 ALOGPS
pKa 18.01 ChemAxon Molconvert
hydrogen acceptor count 5 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 95.94 ChemAxon Molconvert
rotatable bond count 10 ChemAxon Molconvert
refractivity 115.23 ChemAxon Molconvert
polarizability 44.98 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Chan KK, Buch A, Glazer RD, John VA, Barr WH: Site-differential gastrointestinal absorption of benazepril hydrochloride in healthy volunteers. Pharm Res. 1994 Mar;11(3):432-7. Pubmed
  2. De Feo P, Torlone E, Perriello G, Fanelli C, Epifano L, Di Vincenzo A, Modarelli F, Motolese M, Brunetti P, Bolli GB: Short-term metabolic effects of the ACE-inhibitor benazepril in type 2 diabetes mellitus associated with arterial hypertension. Diabete Metab. 1992 Jul-Aug;18(4):283-8. Pubmed
  3. Gengo FM, Brady E: The pharmacokinetics of benazepril relative to other ACE inhibitors. Clin Cardiol. 1991 Aug;14(8 Suppl 4):IV44-50; discussion IV51-5. Pubmed
  4. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW: Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006 Jan 12;354(2):131-40. Pubmed
  5. Ishimitsu T, Akashiba A, Kameda T, Takahashi T, Ohta S, Yoshii M, Minami J, Ono H, Numabe A, Matsuoka H: Benazepril slows progression of renal dysfunction in patients with non-diabetic renal disease. Nephrology (Carlton). 2007 Jun;12(3):294-8. Pubmed
  6. MacNab M, Mallows S: Safety profile of benazepril in essential hypertension. Clin Cardiol. 1991 Aug;14(8 Suppl 4):IV33-7; discussion IV51-5. Pubmed
  7. Szekacs B, Vajo Z, Dachman W: Effect of ACE inhibition by benazepril, enalapril and captopril on chronic and post exercise proteinuria. Acta Physiol Hung. 1996;84(4):361-7. Pubmed
External Links
Resource Link
KEGG Compound C06843 Link_out
PubChem Compound 5362124 Link_out
PubChem Substance 46507884 Link_out
ChemSpider 4514935 Link_out
ChEBI 3011 Link_out
ChEMBL 3011 Link_out
Therapeutic Targets Database DAP000584 Link_out
PharmGKB PA448561 Link_out
Drug Product Database 885835 Link_out
RxList http://www.rxlist.com/cgi/generic/benaz.htm Link_out
Drugs.com http://www.drugs.com/cdi/benazepril.html Link_out
PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=lot1238.html&contentName=Lotensin&contentId=458 Link_out
Wikipedia http://en.wikipedia.org/wiki/Benazepril Link_out
ATC Codes
  • C09AA07
AHFS Codes
  • 24:32.04
PDB Entries
FDA label show (236.9 KB)
MSDS show (57.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Benazepril may decrease the excretion of potassium. Salt um may increase the risk of hyperkalemia. substitutes containing potassi
  • Food slows absorption without decreasing the quantity absorbed.
  • Herbs that may attenuate the antihypertensive effect of benazepril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of benazepril.
  • Take without regard to meals.
Targets

1. Angiotensin-converting enzyme

Pharmacological action: yes
Actions: inhibitor

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 vasodilator

Organism class: human
UniProt ID: P12821 Link_out
Gene: ACE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. 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
Enzymes

1. Methylenetetrahydrofolate reductase

Actions: substrate

Catalyzes the conversion of 5,10- methylenetetrahydrofolate to 5-methyltetrahydrofolate, a co- substrate for homocysteine remethylation to methionine

UniProt ID: P42898 Link_out
Gene: MTHFR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Jiang S, Yu Y, Venners SA, Zhang Y, Xing H, Wang X, Xu X: Effects of MTHFR and MS gene polymorphisms on baseline blood pressure and Benazepril effectiveness in Chinese hypertensive patients. J Hum Hypertens. 2010 May 6. Pubmed
  2. Jiang S, Hsu YH, Niu T, Xu X, Xing H, Chen C, Wang X, Zhang Y, Peng S, Xu X: A common haplotype on methylenetetrahydrofolate reductase gene modifies the effect of angiotensin-converting enzyme inhibitor on blood pressure in essential hypertension patients—a family-based association study. Clin Exp Hypertens. 2005 Aug;27(6):509-21. Pubmed
  3. Jiang S, Hsu YH, Xu X, Xing H, Chen C, Niu T, Zhang Y, Peng S, Xu X: The C677T polymorphism of the methylenetetrahydrofolate reductase gene is associated with the level of decrease on diastolic blood pressure in essential hypertension patients treated by angiotensin-converting enzyme inhibitor. Thromb Res. 2004;113(6):361-9. Pubmed
Transporters

1. Oligopeptide transporter, small intestine isoform

Actions: substrate

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

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Aug 19. Pubmed

2. Oligopeptide transporter, kidney isoform

Actions: substrate

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides

UniProt ID: Q16348 Link_out
Gene: SLC15A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2008 Aug 19. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 07, 2011 15:40

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.