PERINDOPRIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H32N2O5
Molecular Weight	368.4678
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[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=IPVQLZZIHOAWMC-QXKUPLGCSA-N

InChI=1S/C19H32N2O5/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/h12-16,20H,4-11H2,1-3H3,(H,23,24)/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
Pharmacokinetics of perindopril and its metabolites in healthy volunteers.	1990	2351367
The initial hemodynamic response to newer antihypertensive agents at rest and during exercise: review of visacor, doxazosin, nisoldipine, tiapamil, perindoprilat, pinacidil, dilevalol, and carvedilol.	1990 Aug	1964580
Specific and high affinity binding of perindoprilat, but not of perindopril to blood ACE.	1992 Sep	1330941
[Effects of perindopril and its combination with indapamide on risk stratification in patients with hypertension].	2001	11642074
[Effects of perstarium on the systolic and diastolic functions of the myocardium in patients with chronic cardiac failure].	2001	11588778
Hypertension in the Very Elderly Trial (HYVET): protocol for the main trial.	2001	11302283
Microthrombosis in sepsis.	2001 Apr	11376528
Academic support for combination therapy in hypertension.	2001 Aug-Sep	11766616
ACE inhibitors in vascular disease: some PROGRESS, more HOPE.	2001 Dec	11773984
The lowering of blood pressure after stroke.	2001 Dec 8	11747945
The lowering of blood pressure after stroke.	2001 Dec 8	11747943
Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus.	2001 Feb	11181984
Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor.	2001 Jan	11206683
Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.	2001 Jul	11759959
The quantitative determination of several inhibitors of the angiotensin-converting enzyme by CE.	2001 Jul	11377060
[PROGRESS Study examines transient cerebral ischemia and stroke patients. Future goal: attaining basic blood pressure control].	2001 Jul 5	11481915
Effects of an angiotensin-converting enzyme inhibitor and a beta-blocker on cerebral arteriolar dilatation in hypertensive rats.	2001 Jun	11408382
Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.	2001 Jun	11403364
Coversyl plus--when monotherapy is not enough.	2001 Jun-Jul	11710312
Pulmonary vascular remodelling in hypoxic rats: effects of amlodipine, alone and with perindopril.	2001 Mar 23	11282121
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
Effects of combined administration of ACE inhibitor and angiotensin II receptor antagonist are prevented by a high NaCl intake.	2001 Nov	11677376
Perindopril treatment for congestive heart failure.	2001 Oct 4	11591357
Very-low-dose combination of perindopril and indapamide as a novel strategy in first-line management of hypertension.	2001 Sep	11713850
Identification and determination of selected medicines reducing hypertension by densitometric and gas chromatographic methods.	2001 Sep-Oct	11876439
Detection of coronary microvascular disease by means of cardiac scintigraphy.	2002 Feb	11875588
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

Official Name

English

Perindopril [WHO-DD]

Common Name

English

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

Common Name

English

perindopril [INN]

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.))-

Common Name

English

S-9490

Code

English

PERINDOPRIL [MART.]

Common Name

English

PERINDOPRIL [VANDF]

Common Name

English

MCN-A-2833

Code

English

PERINDOPRIL [MI]

Common Name

English

PERINDOPRIL [USAN]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC09AA04