PERINDOPRIL ERBUMINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H32N2O5.C4H11N
Molecular Weight	441.6046
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)N.[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

InChI

InChIKey=IYNMDWMQHSMDDE-MHXJNQAMSA-N

InChI=1S/C19H32N2O5.C4H11N/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;1-4(2,3)5/h12-16,20H,4-11H2,1-3H3,(H,23,24);5H2,1-3H3/t12-,13-,14-,15-,16-;/m0./s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020184s022lbl.pdfhttp://pubs.rsc.org/-/content/getauthorversionpdf/C3AY42056Fhttps://www.ncbi.nlm.nih.gov/pubmed/1457697http://www.hmdb.ca/metabolites/HMDB60574
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/1718688

Perindoprilat is a metabolite of perindopril. Perindopril is a long-acting angiotensin converting enzyme (ACE) inhibitor and it is used to treat high blood pressure, heart failure or stable coronary artery disease. Perindopril is designed to allow oral administration as perindoprilat is poorly absorbed from the gastrointestinal tract.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: http://www.hmdb.ca/metabolites/HMDB60574	Inhibitor 8297		1.05 nM [IC50]
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17716647	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2578
Unknown 2578
Stable coronary artery disease 7 Sources: https://www.drugs.com/pro/perindopril.html	Primary	Approved 8429	ACEON Approved Use Perindopril erbumine tablets are indicated for treatment of patients with stable coronary artery disease to reduce the risk of cardiovascular mortality or nonfatal myocardial infarction. Perindopril erbumine tablets can be used with conventional treatment for management of coronary artery disease, such as antiplatelet, antihypertensive or lipid-lowering therapy. Launch Date 1993
Hypertension 567 Sources: https://www.drugs.com/pro/perindopril.html	Primary	Approved 8429	ACEON Approved Use Perindopril erbumine tablets are indicated for the treatment of patients with essential hypertension. Perindopril erbumine tablets may be used alone or given with other classes of antihypertensives, especially thiazide diuretics. Launch Date 1993
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10800878	Palliative	Not Provided 504	Unknown Approved Use Unknown
Unknown 2578

C_max

Value	Dose	Co-administered	Analyte	Population
83.83 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
3.54 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
130 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
170.61 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.05 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
38.01 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
40% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
80% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/21650082	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		PERINDOPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
4 mg 1 times / day steady, oral Recommended Dose: 4 mg, 1 times / day Route: oral Route: steady Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12076191/	unhealthy, adult n = 320 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Population Size: 320 Sources: https://pubmed.ncbi.nlm.nih.gov/12076191/	Disc. AE: Cough... AEs leading to discontinuation/dose reduction: Cough (2.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/12076191/

AEs

AE	Significance	Dose	Population
Cough	2.8% Disc. AE	4 mg 1 times / day steady, oral Recommended Dose: 4 mg, 1 times / day Route: oral Route: steady Dose: 4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12076191/	unhealthy, adult n = 320 Health Status: unhealthy Condition: hypertension Age Group: adult Sex: unknown Population Size: 320 Sources: https://pubmed.ncbi.nlm.nih.gov/12076191/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2J2 16	UGT 192 CYP 270	CYP 76

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 147	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	no
CYP2J2 19	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0009279719303631	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	no
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020184s023lbl.pdf#page=9 Page: 9.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:132041	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:132041
ChemicalBook	CB0240343	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0240343
MolPort	MolPort-006-395-652	https://www.molport.com/shop/molecule-link/MolPort-006-395-652
ZINC	ZINC000004217270	http://zinc15.docking.org/substances/ZINC000004217270
eMolecules	36754394	https://www.emolecules.com/cgi-bin/more?vid=36754394

PubMed

Title	Date	PubMed
Inhibition of angiotensin I-converting enzyme with S 9490: biochemical effects, interspecies differences, and role of sodium diet in hemodynamic effects.	1984 Nov-Dec	6084763
[The effect of amlodipine, nifedipine and perindopril on insulin sensitivity and blood lipid of patients with essential hypertension].	1998 Mar	10923530
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.	2000 Oct	11007831
Interventions for deliberately altering blood pressure in acute stroke.	2001	11686949
Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study.	2001 Apr	11330885
Indapamide plus perindopril--simpler treatment, better compliance.	2001 Apr-May	11474694
Anglo-Scandinavian Cardiac Outcomes Trial: a brief history, rationale and outline protocol.	2001 Aug	11685901
Effects of ACE inhibitor therapy on derived central arterial waveforms in hypertension.	2001 Aug	11497198
Comparison of spectrophotometric and an LC method for the determination perindopril and indapamide in pharmaceutical formulations.	2001 Aug	11451641
Comparison of endothelial pleiotropic actions of angiotensin converting enzyme inhibitors and statins.	2001 Dec	11795271
ACE inhibitors in vascular disease: some PROGRESS, more HOPE.	2001 Dec	11773984
The lowering of blood pressure after stroke.	2001 Dec 8	11747943
Inhibition of neointima by angiotensin-converting enzyme inhibitor in porcine coronary artery balloon-injury model.	2001 Feb	11230284
Hyperoxia/normoxia-driven retinal angiogenesis in mice: a role for angiotensin II.	2001 Feb	11157878
Effect of perindopril on cerebral and renal perfusion in stroke patients with carotid disease.	2001 Feb	11157185
Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor.	2001 Jan	11206683
Significance of endothelial prostacyclin and nitric oxide in peripheral and pulmonary circulation.	2001 Jan-Feb	11208485
The quantitative determination of several inhibitors of the angiotensin-converting enzyme by CE.	2001 Jul	11377060
Angiotensin converting enzyme inhibitor restrains inflammation-induced vascular injury in mice.	2001 Jun	11403357
Coversyl plus--when monotherapy is not enough.	2001 Jun-Jul	11710312
New benefits of blood pressure lowering treatments for millions of stroke sufferers.	2001 Jun-Jul	11710310
Elimination of early rehospitalization in a randomized, controlled trial of multidisciplinary care in a high-risk, elderly heart failure population: the potential contributions of specialist care, clinical stability and optimal angiotensin-converting enzyme inhibitor dose at discharge.	2001 Mar	11246059
Effect of renin-angiotensin system blockade on the expression of the angiotensinogen gene and induction of hypertrophy in rat kidney proximal tubular cells.	2001 Mar-Apr	11150859
Salt sensitivity in genetically hypertensive rats of the Lyon strain.	2001 May	11318958
Clinical benefit of very-low-dose perindopril-indapamide combination in hypertension.	2001 Nov	11848262
Amelioration of arterial properties with a perindopril-indapamide very-low-dose combination.	2001 Nov	11848258
[Early prevention of experimental left ventricular hypertrophy in experimental hypertension and angiotensin II levels].	2001 Nov	11707239
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.	2001 Nov	11699055
[Efficacy of a converting enzyme inhibitor in the prevention of recurrence of stroke].	2001 Nov 24	11775593
Increased absorption of zinc from alimentary tract in primary arterial hypertension.	2001 Oct	11694000
Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway.	2001 Oct 12	11597990
Efficacy of perindopril in the treatment of systemic hypertension.	2001 Oct 4	11591355
Hypertension. Introduction.	2001 Oct 4	11591354
Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats.	2001 Sep	11716352
Very-low-dose combination of perindopril and indapamide as a novel strategy in first-line management of hypertension.	2001 Sep	11713850
Effect of blood pressure reduction on abnormal left atrial appendage function in untreated systemic hypertensive patients with sinus rhythm.	2001 Sep	11570661
Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack.	2001 Sep 29	11589932
Blood-pressure lowering for the secondary prevention of stroke.	2001 Sep 29	11589927
[Antihypertensive agents after cerebral stroke are more effective than expected].	2001 Sep-Oct	11845587
Progress in secondary prevention of stroke with PROGRESS. The perindopril protection against recurrent stroke study.	2002 Feb	11790290
Attenuation of tubular apoptosis by blockade of the renin-angiotensin system in diabetic Ren-2 rats.	2002 Jan	11786082
Comparison of perindopril versus captopril for treatment of acute myocardial infarction.	2002 Jan 15	11792333
Combined therapy with indapamide and perindopril but not perindopril alone reduced the risk for recurrent stroke.	2002 Mar-Apr	11874276

Patents

Sample Use Guides

In Vivo Use Guide

In patients with essential hypertension, the recommended initial dose is 4 mg once a day. The dose may be titrated, as needed to a maximum of 16 mg per day. The usual maintenance dose range is 4 mg to 8 mg administered as a single daily dose or in two divided doses. In patients with stable coronary artery disease, Perindopril erbumine tablets should be given at an initial dose of 4 mg once daily for 2 weeks, and then increased as tolerated, to a maintenance dose of 8 mg once daily. In elderly patients (greater than 70 years), Perindopril erbumine tablets should be given as a 2 mg dose once daily in the first week, followed by 4 mg once daily in the second week and 8 mg once daily for maintenance dose if tolerated.

Route of Administration: Oral

In Vitro Use Guide

Perindoprilat (S-9780), the major metabolite of perindopril, inhibited guinea pig plasma angiotensin-converting enzyme (ACE) by 50% (IC50) at a concentration of 2.4 +/- 0.1 nM. A Ki of 1.2 nM was obtained for S-9780 (Dixon-Webb plot) with angiotensin I as a substrate.

Name

Type

Language

PERINDOPRIL ERBUMINE

Official Name

English

PERINDOPRIL ERBUMINE [MART.]

Common Name

English

PERINDOPRIL TERT-BUTYLAMINE [EP MONOGRAPH]

Common Name

English

PERINDOPRIL ERBUMINE [USAN]

Common Name

English

PERINDOPRIL ERBUMINE [USP MONOGRAPH]

Common Name

English

Perindopril erbumine [WHO-DD]

Common Name

English

AMLESSA COMPONENT PERINDOPRIL ERBUMINE

Common Name

English

PERINDOPRIL T-BUTYLAMINE

Common Name

English

PERINDOPRIL ERBUMINE [ORANGE BOOK]

Common Name

English

S-9490-3

Code

English

ACEON

Brand Name

English

MCN-A-2833-109

Code

English

NSC-758929

Code

English

(2S,3aS,7aS)-1-[(S)-N-[(S)-1-Carboxybutyl]alanyl]hexahydro-2-indolinecarboxylic acid, 1-ethyl ester, compound with tert-butylamine (1:1)

Common Name

English

1H-INDOLE-2-CARBOXYLIC ACID, 1-(2-((1-(ETHOXYCARBONYL)BUTYL)AMINO)-1-OXOPROPYL)OCTAHYDRO-, (2S-(1(R*(R*)),2.ALPHA.,3A.BETA.,7A.BETA.))-, COMPD. WITH 2-METHYL-2-PROPANAMINE (1:1)

Common Name

English

PERINDOPRIL TERT-BUTYLAMINE

Common Name

English

PERINDOPRIL ERBUMINE [VANDF]

Common Name

English

PERINDOPRIL ERBUMINE [JAN]

Common Name

English

PERINDOPRIL ERBUMINE [USP-RS]

Common Name

English

PERINDOPRIL TERT-BUTYLAMINE [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C247

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Code System Code Type Description

MERCK INDEX

m8555

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Merck Index

RXCUI

72260

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RxNorm

SMS_ID

100000091602

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USAN

AA-67

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EPA CompTox

DTXSID1044198

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EVMPD

SUB03711MIG

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DRUG BANK

DB00790

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RS_ITEM_NUM

1510889

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CAS

107133-36-8

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NSC

758929

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PUBCHEM

441313

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CHEBI

8025

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ChEMBL

CHEMBL1581

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NCI_THESAURUS

C47666

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DAILYMED

1964X464OJ

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FDA UNII

1964X464OJ

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ACTIVE MOIETY


					2UV6ZNQ92K

PERINDOPRILAT

PARENT (SALT/SOLVATE)


					91Z53KF68U

ERBUMINE

PARENT (SALT/SOLVATE)


					Y5GMK36KGY

PERINDOPRIL

SUBSTANCE RECORD


					1964X464OJ

PERINDOPRIL ERBUMINE

Details

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Approved Use

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator