TRANDOLAPRIL

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H34N2O5
Molecular Weight	430.5372
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](CCC3=CC=CC=C3)C(=O)OCC)[C@@]1([H])CCCC2)C(O)=O

InChI

InChIKey=VXFJYXUZANRPDJ-WTNASJBWSA-N

InChI=1S/C24H34N2O5/c1-3-31-24(30)19(14-13-17-9-5-4-6-10-17)25-16(2)22(27)26-20-12-8-7-11-18(20)15-21(26)23(28)29/h4-6,9-10,16,18-21,25H,3,7-8,11-15H2,1-2H3,(H,28,29)/t16-,18+,19-,20-,21-/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00519
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf

Trandolapril is a non-sulhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to its biologically active diacid form, trandolaprilat, in the liver. Trandolaprilat inhibits ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Trandolapril may be used to treat mild to moderate hypertension, to improve survival following myocardial infarction in clinically stable patients with left ventricular dysfunction, as an adjunct treatment for congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy. Trandolapril is marketed by Abbott Laboratories under the brand name Mavik.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Angiotensin-converting enzyme 97 Target ID: CHEMBL1808 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf \| http://www.drugbank.ca/drugs/DB00519	Inhibitor 8297		15.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf	Primary		Approved 8429	MAVIK Approved Use Hypertension MAVIK is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medication such as hydrochlorothiazide. Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction MAVIK is indicated in stable patients who have evidence of left-ventricular systolic dysfunction (identified by wall motion abnormalities) or who are symptomatic from congestive heart failure within the first few days after sustaining acute myocardial infarction. Launch Date 1996
Heart failure post myocardial infarction 3 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020528s024lbl.pdf	Primary		Approved 8429	MAVIK Approved Use Hypertension MAVIK is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive medication such as hydrochlorothiazide. Heart Failure Post Myocardial Infarction or Left-Ventricular Dysfunction Post Myocardial Infarction MAVIK is indicated in stable patients who have evidence of left-ventricular systolic dysfunction (identified by wall motion abnormalities) or who are symptomatic from congestive heart failure within the first few days after sustaining acute myocardial infarction. Launch Date 1996

C_max

Value	Dose	Analyte	Population
9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
0.99 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.3 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.2 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
101 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
19.1 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.8 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	1 mg single, oral dose: 1 mg route of administration: Oral experiment type: SINGLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
8.2 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
115 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TRANDOLAPRILAT plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/96/020528Orig1s000rev.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TRANDOLAPRIL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	Disc. AE: Diarrhea, Dizziness... AEs leading to discontinuation/dose reduction: Diarrhea Dizziness Elevated liver enzymes Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/

AEs

AE	Significance	Dose	Population
Diarrhea	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/
Dizziness	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/
Elevated liver enzymes	Disc. AE	8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/	unhealthy, 55 n = 151 Health Status: unhealthy Condition: hypertension Age Group: 55 Sex: M+F Population Size: 151 Sources: https://pubmed.ncbi.nlm.nih.gov/9231890/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CES1 22 CES2 28

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CES2 28	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24141856/	no	TRANDOLAPRIL 3
CES1 22	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24141856/	yes [Km 1721 uM]	TRANDOLAPRIL 3

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-1477	http://www.3bsc.com/index/pro_info.php?id=55193
Alfa Chemistry	AP87679718	https://reagents.alfa-chemistry.com/product/trandolapril-related-compound-e-cas-87679-71-8-17686.html
Alfa Chemistry	83601-86-9	https://www.alfa-chemistry.com/cas_83601-86-9.htm
BLD Pharm	BD154453	http://www.bldpharm.com/products/87679-71-8.html
ChemMol	49422350	http://www.chemmol.com/chemmol/49422350.html
Clearsynth	CS-O-08347	https://www.clearsynth.com/en/CSO08347.html
DC Chemicals	DC32672	http://www.dcchemicals.com//product_show-Trandolaprilat.html
Excenen	EX-A4862	https://www.excenen.com/searchresultlist.php?id=EX-A4862
Glentham Life Sciences	GP7119	http://www.glentham.com/products/product/GP7119/
MuseChem	R044833	https://www.musechem.com/product/R044833.html
OChem	21859	http://www.ocheminc.com/index.php?act=psearch&pid=679T718
Smolecule	S545706	http://www.smolecule.com/products/s545706
THE BioTek	bt-286404	https://www.thebiotek.com/product/inhibitors/bt-286404
eNovation Chemicals	D591705	https://www.enovationchem.com/ProductDetails.asp?ProductID=D591705
iChemical	EBD21706	http://www.ichemical.com/products/87679-71-8.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
Trandolapril in hypertension: overview of a new angiotensin-converting enzyme inhibitor.	1992 Oct 29	1414922
Effect of two antihypertensive combinations on metabolic control in type-2 diabetic hypertensive patients with albuminuria: a randomised, double-blind study.	2001 Dec	11773987
Early neurohormonal effects of trandolapril in patients with left ventricular dysfunction and a recent acute myocardial infarction: a double-blind, randomized, placebo-controlled multicentre study.	2001 Jan	11163738
Verapamil versus amlodipine in proteinuric non-diabetic nephropathies treated with trandolapril (VVANNTT study): design of a prospective randomized multicenter trial.	2001 Jan-Feb	11281338
[The effect of trandolapril, in monotherapy and associated with verapamil, on arterial pressure, albuminuria, and metabolic control in hypertensive patients with type 2 diabetes and albuminuria].	2001 Sep-Oct	11795014
Using ACE inhibitors appropriately.	2002 Aug 1	12182524
Impact of age and sex on sudden cardiovascular death following myocardial infarction.	2002 Dec	12433881
Acute blood pressure response to trandolapril and captopril in patients with left ventricular dysfunction after acute myocardial infarction.	2002 Feb	11835037
Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: role of vascular superoxide anion formation and endothelial nitric oxide synthase expression.	2002 Jan 16	11788231
Angiotensin II and trials of cardiovascular outcomes.	2002 Jan 24	11835905
Angiotensin-converting enzyme inhibition and endothelin antagonism for endothelial dysfunction in heart failure: mono-or combination therapy.	2002 Oct	12352322
The angiotensin converting enzyme inhibitor trandolapril has neutral effect on exercise tolerance or functional class in patients with myocardial infarction and reduced left ventricular systolic function.	2003 Dec	14643272
ACE inhibition limits chronic injury of kidney transplant even with treatment started when lesions are established.	2003 Dec	14633150
Inhibition of platelet activation in congestive heart failure by aldosterone receptor antagonism and ACE inhibition.	2003 Jun	12783115
Tick-borne encephalitis with hemorrhagic syndrome, Novosibirsk region, Russia, 1999.	2003 Jun	12781020
Addition of the selective aldosterone receptor antagonist eplerenone to ACE inhibition in heart failure: effect on endothelial dysfunction.	2003 Jun 1	12798439
The COOPERATE trial.	2003 Mar 22	12660075
Submaximal dose of trandolapril in the COOPERATE trial?	2003 Nov	14531832
Aldosterone antagonism and myocardial infarction: from animals to man and back.	2003 Nov 5	14607458
Renal damage in the SHR/N-cp type 2 diabetes model: comparison of an angiotensin-converting enzyme inhibitor and endothelin receptor blocker.	2003 Sep	13679434
[Preventive therapy with ACE inhibitors for coronary patients].	2004 Feb 29	15077477
Effects of bedtime vs. morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients.	2004 Jan	15055251
Significant target organs for hypertension and cardiac hypertrophy by angiotensin-converting enzyme inhibitors.	2004 Mar	15080380

Patents

Sample Use Guides

In Vivo Use Guide

The recommended initial dosage of MAVIK (Trandolapril) for patients not receiving a diuretic is 1 mg once daily in non-black patients and 2 mg in black patients.

Route of Administration: Oral

In Vitro Use Guide

Trandolapril at 10(-7) mol/l, significantly increased 11beta-HSD2 activity after pretreatment for 16 or 24 h of the human epithelial colon cell line SW-620

Name

Type

Language

TRANDOLAPRIL

Official Name

English

TRANDOLAPRIL [USP-RS]

Common Name

English

TRANDOLAPRIL [VANDF]

Common Name

English

TRANDOLAPRIL [JAN]

Common Name

English

1H-INDOLE-2-CARBOXYLIC ACID, OCTAHYDRO N-((2S)-1-ETHOXY-1-OXO-4-PHENYLBUTAN-2-YL)-1-ALANYL (2S,3AR,7AS)

Common Name

English

TRANDOLAPRIL [EP MONOGRAPH]

Common Name

English

TRANDOLAPRIL [USP MONOGRAPH]

Common Name

English

TRANDOLAPRIL [MI]

Common Name

English

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

Common Name

English

NSC-758939

Code

English

TRANDOLAPRIL [ORANGE BOOK]

Common Name

English

TARKA COMPONENT TRANDOLAPRIL

Common Name

English

TRANDOLAPRIL COMPONENT OF TARKA

Common Name

English

TRANDOLAPRIL [MART.]

Common Name

English

RU 44570

Code

English

MAVIK

Brand Name

English

Trandolapril [WHO-DD]

Common Name

English

trandolapril [INN]

Common Name

English

RU-44570

Code

English

Classification Tree Code System Code

WHO-VATC

QC09AA10