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 96 Target ID: CHEMBL1808 Sources: http://www.hmdb.ca/metabolites/HMDB60574	Inhibitor 8228		1.05 nM [IC50]
Angiotensin-converting enzyme 96 Target ID: CHEMBL1808 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17716647	Inhibitor 8228

Conditions

Condition	Modality	Highest Phase	Product
Unknown 2565
Unknown 2565
Stable coronary artery disease 7 Sources: https://www.drugs.com/pro/perindopril.html	Primary	Approved 8360	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 7.5720963E11
Hypertension 549 Sources: https://www.drugs.com/pro/perindopril.html	Primary	Approved 8360	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 7.5720963E11
Parkinson's disease 225 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10800878	Palliative	Not Provided 503	Unknown Approved Use Unknown
Unknown 2565

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 187 CYP 266	CYP 76

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 146	inducer 1542 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	no
CYP2J2 19	inhibitor 3240 Sources: https://www.sciencedirect.com/science/article/pii/S0009279719303631	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP 266	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15449971/	no
UGT 187	substrate 3326 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
Challenges for the prevention of primary and secondary stroke: the importance of lowering blood pressure and total cardiovascular risk.	2001	11822538
[Effects of angiotensin-converting enzyme inhibitors and cosaar on quality of life of patients with pulmonary tuberculosis and chronic heart failure].	2001	11767390
[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
Perindopril/indapamide 2/0.625 mg/day: a review of its place in the management of hypertension.	2001	11465878
Perindopril: an updated review of its use in hypertension.	2001	11398915
Microthrombosis in sepsis.	2001 Apr	11376528
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
Combination BP therapy cuts second stroke risk in half.	2001 Aug	11505852
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
Academic support for combination therapy in hypertension.	2001 Aug-Sep	11766616
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
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
Comparison of the effect of perindopril and acebutolol on cerebral hemodynamics in hypertensive patients.	2001 Jan	11504165
Assessment of perindopril's efficacy on arterial distensibility in mild to moderate hypertension.	2001 Jul	11759959
Pharmacokinetic-pharmacodynamic model for perindoprilat regional haemodynamic effects in healthy volunteers and in congestive heart failure patients.	2001 Jul	11453887
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
Angiotensin converting enzyme inhibitor restrains inflammation-induced vascular injury in mice.	2001 Jun	11403357
Angiotensin-converting enzyme inhibitor therapy improves respiratory muscle strength in patients with heart failure.	2001 Jun	11399702
The EUROPA trial: design, baseline demography and status of the substudies.	2001 Mar	11669411
Antihypertensive efficacy and tolerability of low-dose perindopril/indapamide combination compared with losartan in the treatment of essential hypertension.	2001 May	11406907
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
[Clinical study of the month. Secondary prevention of cerebrovascular accident with perindopril: the PROGRESS study].	2001 Nov	11789395
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
A double-blind trial of perindopril and nitrendipine in incipient diabetic nephropathy.	2001 Oct	11806464
Proangiogenic effect of angiotensin-converting enzyme inhibition is mediated by the bradykinin B(2) receptor pathway.	2001 Oct 12	11597990
Perindopril treatment for congestive heart failure.	2001 Oct 4	11591357
Hypertension. Introduction.	2001 Oct 4	11591354
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
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
Comparison of perindopril versus captopril for treatment of acute myocardial infarction.	2002 Jan 15	11792333
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