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Details

Stereochemistry RACEMIC
Molecular Formula C24H26N2O4.H3O4P
Molecular Weight 504.4694
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARVEDILOL PHOSPHATE ANHYDROUS

SMILES

OP(O)(O)=O.COC1=C(OCCNCC(O)COC2=CC=CC3=C2C4=C(N3)C=CC=C4)C=CC=C1

InChI

InChIKey=XCPXNPBILMXKNX-UHFFFAOYSA-N
InChI=1S/C24H26N2O4.H3O4P/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20;1-5(2,3)4/h2-12,17,25-27H,13-16H2,1H3;(H3,1,2,3,4)

HIDE SMILES / InChI

Molecular Formula C24H26N2O4
Molecular Weight 406.4742
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Molecular Formula H3O4P
Molecular Weight 97.9952
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Carvedilol competitively blocks β1, β2 and α1 receptors. The drug lacks sympathomimetic activity and has vasodilating properties that are exerted primarily through α1-blockade. Animal models indicate that carvedilol confers protection against myocardial necrosis, arrhythmia and cell damage caused by oxidising free radicals, and the drug has no adverse effects on plasma lipid profiles. COREG® (carvedilol) is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α1-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol is the first drug of its kind to be approved for the treatment of congestive heart failure, and is now the standard of care for this devastating disease. Carvedilol is also confirmed as effective in the management of mild to moderate hypertension and ischaemic heart disease.

Originator

Curator's Comment: reference retrieved from http://www.drugfuture.com/chemdata/carvedilol.html

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
COREG

Approved Use

COREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization. COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure). COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

1995
Primary
COREG

Approved Use

COREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization. COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure). COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

1995
Primary
COREG

Approved Use

COREG® (carvedilol) is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization. COREG is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of ≤40% (with or without symptomatic heart failure). COREG is indicated for the management of essential hypertension. It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics.

Launch Date

1995
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
18.4 ng/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (+)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
8.46 ng/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (-)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
26.5 ng/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
94.3 ng × h/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (+)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
42.2 ng × h/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL, (-)- plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
139 ng × h/mL
6.25 mg 2 times / day steady-state, oral
dose: 6.25 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
CARVEDILOL plasma
Homo sapiens
population: UNHEALTHY
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Co-administed with::
lorazepam(7 mg)
Sources:
unknown, 41 years
n = 1
Health Status: unknown
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Other AEs: Wheezing...
Other AEs:
Wheezing (1 patient)
Sources:
80 mg 1 times / day multiple, oral
Highest studied dose
Dose: 80 mg, 1 times / day
Route: oral
Route: multiple
Dose: 80 mg, 1 times / day
Sources:
unhealthy, 66.7±12.0 years
n = 7
Health Status: unhealthy
Condition: chronic heart failure
Age Group: 66.7±12.0 years
Sex: M+F
Population Size: 7
Sources:
375 mg single, oral
Overdose
Dose: 375 mg
Route: oral
Route: single
Dose: 375 mg
Co-administed with::
simvastatin(fifteen 20-mg tablets)
Sources:
unhealthy, 84 years
n = 1
Health Status: unhealthy
Age Group: 84 years
Sex: M
Population Size: 1
Sources:
Other AEs: Hypotension...
Other AEs:
Hypotension (1 patient)
Sources:
50 mg 1 times / day steady, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
n = 765
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Population Size: 765
Sources:
Disc. AE: Hypotension...
AEs leading to
discontinuation/dose reduction:
Hypotension (0.7%)
Sources:
20 mg 2 times / day multiple, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Disc. AE: Congestive cardiac failure...
AEs leading to
discontinuation/dose reduction:
Congestive cardiac failure (moderate, 1 patient)
Sources: Page: p. 61
25 mg 2 times / day steady, oral
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, adult
n = 1156
Health Status: unhealthy
Condition: severe heart failure
Age Group: adult
Population Size: 1156
Sources:
Disc. AE: Dizziness...
AEs leading to
discontinuation/dose reduction:
Dizziness (1.3%)
Sources:
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Disc. AE: Abdominal distension...
AEs leading to
discontinuation/dose reduction:
Abdominal distension (1 patient)
Sources: Page: p. 61
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Disc. AE: Rash...
AEs leading to
discontinuation/dose reduction:
Rash (moderate, 1 patient)
Sources: Page: p. 61
AEs

AEs

AESignificanceDosePopulation
Wheezing 1 patient
300 mg single, oral
Overdose
Dose: 300 mg
Route: oral
Route: single
Dose: 300 mg
Co-administed with::
lorazepam(7 mg)
Sources:
unknown, 41 years
n = 1
Health Status: unknown
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Hypotension 1 patient
375 mg single, oral
Overdose
Dose: 375 mg
Route: oral
Route: single
Dose: 375 mg
Co-administed with::
simvastatin(fifteen 20-mg tablets)
Sources:
unhealthy, 84 years
n = 1
Health Status: unhealthy
Age Group: 84 years
Sex: M
Population Size: 1
Sources:
Hypotension 0.7%
Disc. AE
50 mg 1 times / day steady, oral
Recommended
Dose: 50 mg, 1 times / day
Route: oral
Route: steady
Dose: 50 mg, 1 times / day
Sources:
unhealthy, adult
n = 765
Health Status: unhealthy
Condition: heart failure
Age Group: adult
Population Size: 765
Sources:
Congestive cardiac failure moderate, 1 patient
Disc. AE
20 mg 2 times / day multiple, oral
Dose: 20 mg, 2 times / day
Route: oral
Route: multiple
Dose: 20 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Dizziness 1.3%
Disc. AE
25 mg 2 times / day steady, oral
Dose: 25 mg, 2 times / day
Route: oral
Route: steady
Dose: 25 mg, 2 times / day
Sources:
unhealthy, adult
n = 1156
Health Status: unhealthy
Condition: severe heart failure
Age Group: adult
Population Size: 1156
Sources:
Abdominal distension 1 patient
Disc. AE
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
Rash moderate, 1 patient
Disc. AE
6.25 mg 2 times / day multiple, oral
Dose: 6.25 mg, 2 times / day
Route: oral
Route: multiple
Dose: 6.25 mg, 2 times / day
Sources: Page: p. 61
unhealthy, adult
n = 54
Health Status: unhealthy
Age Group: adult
Population Size: 54
Sources: Page: p. 61
PubMed

PubMed

TitleDatePubMed
Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats.
1999
Beta-blocker selectivity at cloned human beta 1- and beta 2-adrenergic receptors.
1999 Apr
Carvedilol prevents remodeling in patients with left ventricular dysfunction after acute myocardial infarction.
1999 Apr
Potent and selective human beta(3)-adrenergic receptor antagonists.
1999 Aug
Hypotension with dobutamine: beta-adrenergic antagonist selectivity at low doses of carvedilol.
1999 Dec
Carvedilol and lacidipine prevent cardiac hypertrophy and endothelin-1 gene overexpression after aortic banding.
1999 Dec
Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity.
1999 Dec 1
Statins and peripheral neuropathy.
1999 Jan
Treatment with inverse agonists enhances baseline atrial contractility in transgenic mice with chronic beta2-adrenoceptor activation.
1999 Jul
The pharmacokinetics of carvedilol and its metabolites after single and multiple dose oral administration in patients with hypertension and renal insufficiency.
1999 Jun
Cost effectiveness of carvedilol for heart failure.
1999 Mar 15
Beta-blockade in heart failure: a comparison of carvedilol with metoprolol.
1999 Nov 1
Carvedilol reduces ischaemic skeletal muscle necrosis.
1999 Sep
Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol.
1999 Sep
Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites.
2000 Apr
Coordinate regulation of metabolic enzyme encoding genes during cardiac development and following carvedilol therapy in spontaneously hypertensive rats.
2000 Feb
Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway.
2000 Feb
Differential remodeling of the left and right heart after norepinephrine treatment in rats: studies on cytokines and collagen.
2000 Feb
Carvedilol affects the physiological and behavioral response to smoked cocaine in humans.
2000 Jul 1
Beta-blockade in adriamycin-induced cardiomyopathy.
2000 Jun
Levosimendan.
2001
[Comparison of carvedilol and atenolol efficacy in patients with stable effort angina].
2001
Reducing readmissions for congestive heart failure.
2001 Apr 15
Development of a capillary electrophoresis assay for the determination of carvedilol enantiomers in serum using cyclodextrins.
2001 Feb
Variceal bleeding and portal hypertension: still a therapeutic challenge?
2001 Feb
[Economic study of carvedilol in heart failure. A cost effectiveness study in France].
2001 Feb
Differential effects of carvedilol and metoprolol on isoprenaline-induced changes in beta-adrenoceptor density and systolic function in rat cardiac myocytes.
2001 Feb 1
Inhibitory effect of carvedilol in the high-conductance state of the mitochondrial permeability transition pore.
2001 Feb 2
Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study.
2001 Feb 27
Impressive amelioration of clinical (NYHA class) and echocardiographic parameters in heart failure patients treated with amiodarone and carvedilol.
2001 Jan
Effect of fluoxetine on carvedilol pharmacokinetics, CYP2D6 activity, and autonomic balance in heart failure patients.
2001 Jan
beta(1)-Adrenoceptors compensate for beta(3)-adrenoceptors in ileum from beta(3)-adrenoceptor knock-out mice.
2001 Jan
Antioxidant properties of carvedilol and metoprolol in heart failure: a double-blind randomized controlled trial.
2001 Jan
Iodine-123 MIBG imaging before treatment of heart failure with carvedilol to predict improvement of left ventricular function and exercise capacity.
2001 Jan-Feb
Stereoselective effects of (R)- and (S)-carvedilol in humans.
2001 Jul
Influence of carvedilol on the benefits of physical training in patients with moderate chronic heart failure.
2001 Jun
Beta-blockade in chronic heart failure.
2001 Jun 12
[Options in drug combinations].
2001 Mar
Determination of carvedilol in human cardiac tissue by high-performance liquid chromatography.
2001 Mar
Racial differences in the response to drugs--pointers to genetic differences.
2001 May 3
Current role of beta-adrenergic blockers in the management of chronic heart failure.
2001 May 7
Patents

Sample Use Guides

Take with food. Individualize dosage and monitor during up-titration.• Heart failure: Start at 3.125 mg twice daily and increase to 6.25, 12.5, and then 25 mg twice daily over intervals of at least 2 weeks. Maintain lower doses if higher doses are not tolerated.• Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then 25 mg twice daily afterintervals of 3 to 10 days. A lower starting dose or slower titration may be used.• Hypertension: Start at 6.25 mg twice daily and increase if needed for blood pressure control to 12.5 mg then 25 mg twice daily over intervals of 1 to 2 weeks.
Route of Administration: Oral
Compared with the PDGF-stimulated control, DNA synthesis decreased significantly to 60.3% +/- 10.4% and 18.3% +/- 5.9% in the presence of 1 and 10 microM of carvedilol, respectively (P < 0.05, each). Carvedilol significantly inhibited the activity of VSMCs stimulated by ET-1 and ANG-II. The IC50 of carvedilol was 1-10 microM. CsA only inhibited VSMCs significantly in the PDGF-stimulated subgroup. The addition of CsA in the presence of carvedilol did not affect the inhibitory activity of carvedilol. The pattern of inhibition in the combined group was uniform and similar to that of the carvedilol alone group, regardless of the stimulator used.
Substance Class Chemical
Created
by admin
on Sat Dec 16 07:38:20 GMT 2023
Edited
by admin
on Sat Dec 16 07:38:20 GMT 2023
Record UNII
15DX7Y16JB
Record Status Validated (UNII)
Record Version
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Name Type Language
CARVEDILOL PHOSPHATE ANHYDROUS
Common Name English
(2RS)-1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO)PROPAN-2-OL PHOSPHATE SALT (1:1)
Common Name English
2-PROPANOL, 1-(9H-CARBAZOL-4-YLOXY)-3-((2-(2-METHOXYPHENOXY)ETHYL)AMINO)-, PHOSPHATE (1:1)
Systematic Name English
Code System Code Type Description
CAS
374779-45-0
Created by admin on Sat Dec 16 07:38:20 GMT 2023 , Edited by admin on Sat Dec 16 07:38:20 GMT 2023
PRIMARY
PUBCHEM
9827459
Created by admin on Sat Dec 16 07:38:20 GMT 2023 , Edited by admin on Sat Dec 16 07:38:20 GMT 2023
PRIMARY
FDA UNII
15DX7Y16JB
Created by admin on Sat Dec 16 07:38:20 GMT 2023 , Edited by admin on Sat Dec 16 07:38:20 GMT 2023
PRIMARY
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