PERINDOPRILAT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H28N2O5
Molecular Weight	340.4146
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)=O)[C@@]1([H])CCCC2)C(O)=O

InChI

InChIKey=ODAIHABQVKJNIY-PEDHHIEDSA-N

InChI=1S/C17H28N2O5/c1-3-6-12(16(21)22)18-10(2)15(20)19-13-8-5-4-7-11(13)9-14(19)17(23)24/h10-14,18H,3-9H2,1-2H3,(H,21,22)(H,23,24)/t10-,11-,12-,13-,14-/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
[Effects of angiotensin-converting enzyme inhibitors and cosaar on quality of life of patients with pulmonary tuberculosis and chronic heart failure].	2001	11767390
[Hypotension followed the first dose of angiotensin-converting enzyme inhibitor in patients with heart failure (a multicenter clinical trial)].	2001	11642085
[Effects of perindopril and its combination with indapamide on risk stratification in patients with hypertension].	2001	11642074
[The comparison of clinical effectiveness of perindopril and acebutolol in the primary hypertension treatment].	2001	11603173
Vasoactive peptides and procollagen propeptides in patients with hypertension in relation to cardiac hypertrophy and diastolic heart failure: design of the study and patient characteristics.	2001 Aug	11685903
Anglo-Scandinavian Cardiac Outcomes Trial: a brief history, rationale and outline protocol.	2001 Aug	11685901
Persistent cardiovascular effects of chronic renin-angiotensin system inhibition following withdrawal in adult spontaneously hypertensive rats.	2001 Aug	11518847
Combination BP therapy cuts second stroke risk in half.	2001 Aug	11505852
Academic support for combination therapy in hypertension.	2001 Aug-Sep	11766616
ACE inhibitors in vascular disease: some PROGRESS, more HOPE.	2001 Dec	11773984
Chronic ACE inhibition enhances the endothelial control of arterial mechanics and flow-dependent vasodilatation in heart failure.	2001 Dec 1	11751733
The lowering of blood pressure after stroke.	2001 Dec 8	11747948
The lowering of blood pressure after stroke.	2001 Dec 8	11747946
The lowering of blood pressure after stroke.	2001 Dec 8	11747945
The lowering of blood pressure after stroke.	2001 Dec 8	11747944
The lowering of blood pressure after stroke.	2001 Dec 8	11747943
Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.	2001 Jul	11759959
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
The EUROPA trial: design, baseline demography and status of the substudies.	2001 Mar	11669411
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
Effect of angiotensin-converting enzyme inhibition on renal filtration surface area in hypertensive rats.	2001 Nov	11703601
Does ACE inhibition slow progression of glomerulopathy in patients with Type 2 diabetes mellitus?	2001 Nov	11703440
Effects of combined administration of ACE inhibitor and angiotensin II receptor antagonist are prevented by a high NaCl intake.	2001 Nov	11677376
[Efficacy of a converting enzyme inhibitor in the prevention of recurrence of stroke].	2001 Nov 24	11775593
A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy.	2001 Oct	11806464
Increased absorption of zinc from alimentary tract in primary arterial hypertension.	2001 Oct	11694000
Improvement in blood pressure, arterial stiffness and wave reflections with a very-low-dose perindopril/indapamide combination in hypertensive patient: a comparison with atenolol.	2001 Oct	11641310
Angiotensin-II type 1 receptor interaction is a major regulator for liver fibrosis development in rats.	2001 Oct	11584371
Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway.	2001 Oct 12	11597990
Safety profile of perindopril.	2001 Oct 4	11591359
Efficacy of perindopril in the treatment of systemic hypertension.	2001 Oct 4	11591355
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
Renin-angiotensin system is involved in the mechanism of increased serum asymmetric dimethylarginine in essential hypertension.	2001 Sep	11548874
Restenotic process and DD genotype after angiotensin-converting enzyme inhibitor treatment.	2001 Sep 1	11556342
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
Identification and determination of selected medicines reducing hypertension by densitometric and gas chromatographic methods.	2001 Sep-Oct	11876439
[Antihypertensive agents after cerebral stroke are more effective than expected].	2001 Sep-Oct	11845587
Detection of coronary microvascular disease by means of cardiac scintigraphy.	2002 Feb	11875588
Progress in secondary prevention of stroke with PROGRESS. The perindopril protection against recurrent stroke study.	2002 Feb	11790290
Long-term treatment with perindopril ameliorates dobutamine-induced myocardial ischemia in patients with coronary artery disease.	2002 Jan	11855668
Attenuation of tubular apoptosis by blockade of the renin-angiotensin system in diabetic Ren-2 rats.	2002 Jan	11786082
The PROGRESS Trial: preventing strokes by lowering blood pressure in patients with cerebral ischemia. Emerging therapies: critique of an important advance.	2002 Jan	11779934
Effects of low-dose and early versus late perindopril treatment on the progression of severe diabetic nephropathy in (mREN-2)27 rats.	2002 Mar	11856772
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

PERINDOPRILAT

Official Name

English

perindoprilat [INN]

Common Name

English

PERINDOPRIL TERT-BUTYLAMINE IMPURITY B [EP IMPURITY]

Common Name

English

(2S,3AS,7AS)-1-((S)-N-((S)-1-CARBOXYBUTYL)ALANYL)HEXAHYDRO-2-INDOLINECARBOXYLIC ACID

Common Name

English

PERINDOPRIL RELATED COMPOUND B

Common Name

English

PERINDOPRIL RELATED COMPOUND B [USP-RS]

Common Name

English

PERINDOPRIL DIACID FORM [MI]

Common Name

English

PERINDOPRIL DIACID FORM

Common Name

English

S-9780

Code

English

Classification Tree Code System Code

NDF-RT

N0000175562