U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C18H19Cl2NO4
Molecular Weight 384.254
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FELODIPINE

SMILES

CCOC(=O)C1=C(C)NC(C)=C(C1C2=C(Cl)C(Cl)=CC=C2)C(=O)OC

InChI

InChIKey=RZTAMFZIAATZDJ-UHFFFAOYSA-N
InChI=1S/C18H19Cl2NO4/c1-5-25-18(23)14-10(3)21-9(2)13(17(22)24-4)15(14)11-7-6-8-12(19)16(11)20/h6-8,15,21H,5H2,1-4H3

HIDE SMILES / InChI

Molecular Formula C18H19Cl2NO4
Molecular Weight 384.254
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/felodipine.html

Felodipine is a long-acting 1,4-dihydropyridine calcium channel blocker (CCB)b. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, felodipine prevents calcium-dependent myocyte contraction and vasoconstriction. Felodipine is the most potent CCB in use and is unique in that it exhibits fluorescent activity. In addition to binding to L-type calcium channels, felodipine binds to a number of calcium-binding proteins, exhibits competitive antagonism of the mineralcorticoid receptor, inhibits the activity of calmodulin-dependent cyclic nucleotide phosphodiesterase, and blocks calcium influx through voltage-gated T-type calcium channels. Felodipine is used to treat mild to moderate essential hypertension.

CNS Activity

Curator's Comment: Animal studies have demonstrated that felodipine crosses the blood-brain barrier and the placenta.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PLENDIL

Approved Use

PLENDIL is indicated for the treatment of hypertension, to lower blood pressure.

Launch Date

6.8031362E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
23.1 nM
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6.2 nM
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.1 nM
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
35.6 nM
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEHYDROFELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
100.9 nM × h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
33.7 nM × h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
87.5 nM × h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
142 nM × h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DEHYDROFELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
23.1 h
10 mg 2 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: FEMALE / MALE
food status: FASTED
14.1 h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
27.5 h
5 mg 2 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
FELODIPINE plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Disc. AE: Headache, Ankle edema...
AEs leading to
discontinuation/dose reduction:
Headache (18%)
Ankle edema (6%)
Flushing (6%)
Nausea (2%)
Palpitation (2%)
Vertigo (2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Headache 18%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Nausea 2%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Palpitation 2%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Vertigo 2%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Ankle edema 6%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Flushing 6%
Disc. AE
20 mg 1 times / day multiple, oral
Highest studied dose
Dose: 20 mg, 1 times / day
Route: oral
Route: multiple
Dose: 20 mg, 1 times / day
Sources:
unhealthy, 51.5 (39-68)
n = 50
Health Status: unhealthy
Condition: hypertension
Age Group: 51.5 (39-68)
Sex: M+F
Population Size: 50
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 0.726 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
yes
yes
yes
yes (co-administration study)
Comment: Co-administration of another extended release formulation of felodipine with itraconazole resulted in approximately 8-fold increase in the AUC, more than 6-fold increase in the Cmax, and 2-fold prolongation in the half-life of felodipine.
Page: 6.0
PubMed

PubMed

TitleDatePubMed
Baroreflex control of renin release in spontaneously hypertensive rats after administration of felodipine.
1987
Cardiovascular-risk reduction: initial diuretic therapy compared with calcium-antagonist (felodipine) therapy for primary hypertension.
1989 Sep 4
The influence of infusion rate on the hemodynamic effects of felodipine.
1990 Sep
Felodipine in combination with a beta-adrenoceptor blocker as an effective substitute for triple therapy in severe hypertension. The Australian Felodipine Multicentre Study Group.
1991
Long-term effects of felodipine in patients with reduced renal function.
1992 May
General toxicity of the new calcium antagonist felodipine in dogs.
1993 Jul
A multicenter comparison of isradipine and felodipine in the treatment of mild-to-moderate hypertension. The Physician's Study Group.
1993 Mar
Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension.
1994 Jul-Aug
Isradipine. An update of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the treatment of mild to moderate hypertension.
1995 Apr
Global efficacy and tolerability of losartan, an angiotensin II subtype 1-receptor antagonist, in the treatment of hypertension.
1996
A comparison of nisoldipine coat-core and felodipine in the treatment of mild-to-moderate hypertension.
1998 Jun
Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: a randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events. The International Study Group.
1998 Sep
Losartan: a review of its use, with special focus on elderly patients.
2000 Mar
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Optimal treatment of obesity-related hypertension: the Hypertension-Obesity-Sibutramine (HOS) study.
2007 Apr 17
Lercanidipine in the treatment of hypertension.
2007 Mar
A cell protection screen reveals potent inhibitors of multiple stages of the hepatitis C virus life cycle.
2010 Feb 23
Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11).
2013 Dec
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Hypertension Initial dose: 5 mg orally once a day Maintenance dose: 2.5 to 10 mg orally once a day
Route of Administration: Oral
In Vitro Use Guide
the maximum contraction to NA in rat vessels exposed to felodipine (0.1 umol/L) was reduced by 37%, and the contraction to K+ (62 mmol/L) was reduced by 84% compared with vehicle-treated arteries.
Substance Class Chemical
Created
by admin
on Fri Dec 16 16:18:05 UTC 2022
Edited
by admin
on Fri Dec 16 16:18:05 UTC 2022
Record UNII
OL961R6O2C
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FELODIPINE
EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
PLENDIL
Brand Name English
FELODIPINE [USP-RS]
Common Name English
FELODIPINE [MART.]
Common Name English
NSC-760343
Code English
FELODIPINE [VANDF]
Common Name English
Felodipine [WHO-DD]
Common Name English
3,5-PYRIDINEDICARBOXYLIC ACID 4-(2,3-DICHLOROPHENYL)-1,4-DIHYDRO-2,6-DIMETHYL-, ETHYL METHYL ESTER, (±)-
Common Name English
FELODIPINE [ORANGE BOOK]
Common Name English
FELODIPINE [USAN]
Common Name English
FELODIPINE [EP MONOGRAPH]
Common Name English
FELODIPINE [USP MONOGRAPH]
Common Name English
FELODIPINE [MI]
Common Name English
LEXXEL COMPONENT FELODIPINE
Common Name English
FELODIPINE COMPONENT OF LEXXEL
Common Name English
C08CA02
Code English
H 154/82
Code English
felodipine [INN]
Common Name English
(±)-ETHYL METHYL 4-(2,3-DICHLOROPHENYL)-1,4-DIHYDRO-2,6-DIMETHYL-3,5-PYRIDINEDICARBOXYLATE
Systematic Name English
FELODIPINE [USP IMPURITY]
Common Name English
FELODIPINE [JAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C333
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
WHO-ATC C08CA02
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
WHO-VATC QC09BB05
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
WHO-VATC QC08CA02
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
NDF-RT N0000007556
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
LIVERTOX NBK548294
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
NDF-RT N0000175421
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
NDF-RT N0000000069
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
WHO-ATC C09BB05
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
Code System Code Type Description
NSC
760343
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
CAS
72509-76-3
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
MERCK INDEX
M5257
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY Merck Index
WIKIPEDIA
FELODIPINE
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
DRUG BANK
DB01023
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
DRUG CENTRAL
1142
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
RXCUI
4316
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY RxNorm
MESH
D015736
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
PUBCHEM
3333
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
EPA CompTox
DTXSID4023042
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
RS_ITEM_NUM
1269389
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
EVMPD
SUB11963MIG
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
LACTMED
Felodipine
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
INN
4877
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
DAILYMED
OL961R6O2C
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
CHEBI
585948
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
USAN
X-2
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
FDA UNII
OL961R6O2C
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
IUPHAR
4190
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
ChEMBL
CHEMBL1480
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
NCI_THESAURUS
C29046
Created by admin on Fri Dec 16 16:18:05 UTC 2022 , Edited by admin on Fri Dec 16 16:18:05 UTC 2022
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INHIBITOR
IC50
TRANSPORTER -> INHIBITOR
BINDER->LIGAND
BINDING
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
TARGET -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC