AMLODIPINE

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H25ClN2O5
Molecular Weight	408.876
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)C1=C(COCCN)NC(C)=C(C1C2=CC=CC=C2Cl)C(=O)OC

InChI

InChIKey=HTIQEAQVCYTUBX-UHFFFAOYSA-N

InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf

Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular mooth muscle cells than on cardiac muscle cells. Amlodipine is indicated for the treatment of hypertension and coronary artery disease.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Voltage-gated L-type calcium channel alpha-1C subunit 44 Target ID: CHEMBL1940 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/2554708	Antagonist 2849		57.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 575 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	Primary	Approved 8583	NORVASC Approved Use Amlodipine besylate tablets USP are calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: •Hypertension (1.1) о Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. •Coronary Artery Disease (1.2) о Chronic Stable Angina о Vasospastic Angina (Prinzmetal's or Variant Angina) о Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% 1.1 Hypertension Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine besylate. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine besylate tablets USP may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine besylate tablets USP are indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets USP may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal's or Variant Angina) Amlodipine besylate tablets USP are indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets USP may be used as monotherapy or in combination with other antianginal agents. Angiographically Documented CAD In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate tablets USP are indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. Launch Date 1992
Coronary artery disease 48 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	Primary	Approved 8583	NORVASC Approved Use Amlodipine besylate tablets USP are calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: •Hypertension (1.1) о Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. •Coronary Artery Disease (1.2) о Chronic Stable Angina о Vasospastic Angina (Prinzmetal's or Variant Angina) о Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40% 1.1 Hypertension Amlodipine besylate tablets USP are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including amlodipine besylate. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Amlodipine besylate tablets USP may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Amlodipine besylate tablets USP are indicated for the symptomatic treatment of chronic stable angina. Amlodipine besylate tablets USP may be used alone or in combination with other antianginal agents. Vasospastic Angina (Prinzmetal's or Variant Angina) Amlodipine besylate tablets USP are indicated for the treatment of confirmed or suspected vasospastic angina. Amlodipine besylate tablets USP may be used as monotherapy or in combination with other antianginal agents. Angiographically Documented CAD In patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, amlodipine besylate tablets USP are indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure. Launch Date 1992
Chagas disease 19 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25033456	Primary	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
3 μg/L REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
5.9 μg/L REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
10.4 μg/L REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
2.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7867683	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
10.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
187 μg × h/L REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
238 μg × h/L REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
464 μg × h/L REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
114 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7867683	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
169 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
214 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
48 h REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
36 h REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
37 h REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003	20 mg single, oral dose: 20 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
41 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
47 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8112371	5 mg 1 times / day steady-state, oral dose: 5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMLODIPINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% REVIEW https://link.springer.com/article/10.2165%2F00003088-199222010-00003			AMLODIPINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
75 mg single, oral Overdose Dose: 75 mg Route: oral Route: single Dose: 75 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9220044/	unhealthy, 42 years Health Status: unhealthy Age Group: 42 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/9220044/	Disc. AE: Sinus tachycardia, Metabolic acidosis... AEs leading to discontinuation/dose reduction: Sinus tachycardia (1 patient) Metabolic acidosis (1 patient) Hypocalcemia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/9220044/
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	DLT: Edema, Dizziness... Dose limiting toxicities: Edema (10.8%) Dizziness (3.4%) Flushing (2.6%) Palpitation (4.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf
10 mg 1 times / day steady, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: steady Dose: 10 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	Disc. AE: Headache... AEs leading to discontinuation/dose reduction: Headache (1.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf
2.5 mg 1 times / day steady, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: steady Dose: 2.5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	DLT: Edema, Dizziness... Dose limiting toxicities: Edema (1.8%) Dizziness (1.1%) Flushing (0.7%) Palpitation (0.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf
5 mg 1 times / day steady, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: steady Dose: 5 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	DLT: Edema, Dizziness... Dose limiting toxicities: Edema (3%) Dizziness (3.4%) Flushing (1.4%) Palpitation (1.4%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf
5.6 mg 1 times / day steady, oral Recommended Dose: 5.6 mg, 1 times / day Route: oral Route: steady Dose: 5.6 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31345083/	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/31345083/	Other AEs: Neonatal disorder NOS... Other AEs: Neonatal disorder NOS (11 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/31345083/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946 inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP4 290 CYP1A1 132 CYP1A2 2153 CYP2A6 879 CYP2B6 926 CYP2C19 2057 CYP2E1 1060 CYP3A5 136 CYP2C8 1057 P-gp 1741 BCRP 910 OATP1B1 1079 OATP1B3 961 BSEP 550 MRP2 499 MRP3 246	CYP3A 220 CYP2B6 776 CYP3A5 446 P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 985	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/22200670/	moderate [IC50 11.3 uM]
BSEP 554	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP2 625	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 326	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 345	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	no
CYP1A1 272	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	strong [Ki 0.13 uM]
CYP2B6 1160	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/\| https://pubmed.ncbi.nlm.nih.gov/17101742/	strong [Ki 1.95 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	strong
CYP2D6 2546	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/ \| https://pubmed.ncbi.nlm.nih.gov/10640508/	weak [IC50 57 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	weak
CYP2A6 911	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	weak
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	weak
CYP3A4 2633	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210045s000lbl.pdf#page=24, https://pubmed.ncbi.nlm.nih.gov/10805063/ Page: (Label 2) 24	weak	yes (co-administration study) Comment: A prospective study in renal transplant patients (N=11) showed on an average of 40% increase in trough cyclosporine levels when concomitantly treated with amlodipine. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210045s000lbl.pdf#page=24, https://pubmed.ncbi.nlm.nih.gov/10805063/ Page: (Label 2) 24
P-gp 1932	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11145223/, https://go.drugbank.com/drugs/DB00381	yes [IC50 22 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3830936/, https://go.drugbank.com/drugs/DB00381, https://pubmed.ncbi.nlm.nih.gov/15601807/	yes [Inhibition 2 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
OATP1B3 970	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
CYP3A5 201	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210045s000lbl.pdf#page=24 Page: (Label 2) 24	yes	yes (co-administration study) Comment: A prospective study in healthy Chinese volunteers (N=9) with CYP3A5 expressers showed a 2.5-to 4-fold increase in tacrolimus exposure when concomitantly administered with amlodipine. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210045s000lbl.pdf#page=24 Page: (Label 2) 24

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/22909231/, https://go.drugbank.com/drugs/DB00381	likely
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210045Orig1s000ClinPharmR.pdf#page=8 Page: (Label) 8	major
CYP3A 220	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205003Orig1s000ClinPharmR.pdf#page=26 Page: (ClinPharm) 21, 26, (Label 2) 23	major	yes (co-administration study) Comment: Co-administration of the moderate CYP3A inhibitor diltiazem increases the exposure to amlodipine 1.6-fold., Erythromycin co-administration in healthy volunteers did not significantly change amlodipine systemic exposure. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/205003Orig1s000ClinPharmR.pdf#page=26 Page: (ClinPharm) 21, 26, (Label 2) 23
CYP3A5 446	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/28259948/, https://go.drugbank.com/drugs/DB00381	yes	yes (pharmacogenomic study) Comment: Following administration of amlodipine, blood pressure in all patients decreased. The magnitude of the change in blood pressure varied among patients. Individuals with the CYP3A51/3 polymorphism exhibited the highest change in blood pressure, followed by CYP3A54, CYP3A51/1, and CYP3A56 Sources: https://pubmed.ncbi.nlm.nih.gov/28259948/, https://go.drugbank.com/drugs/DB00381
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16869811/, https://go.drugbank.com/drugs/DB00381	yes	yes (pharmacogenomic study) Comment: Amlodipine pharmacokinetics was affected by the genetic polymorphisms of the ABCB1 gene in humans. Sources: https://pubmed.ncbi.nlm.nih.gov/16869811/, https://go.drugbank.com/drugs/DB00381

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTQ5MSJ9fQ%3D%3D

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2668	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2668
eMolecules	901374	https://www.emolecules.com/cgi-bin/more?vid=901374
Selleck Chemicals	Amlodipine(Norvasc)	http://www.selleckchem.com/products/Amlodipine(Norvasc).html

PubMed

Title	Date	PubMed
A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure.	1991	1839434
The unique binding properties of amlodipine: a long-acting calcium antagonist.	1991 Aug	1834847
Pharmacologic characterization of FR172516: a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent.	1999 Apr	10218729
Amlodipine treatment of cocaine dependence.	1999 Apr-Jun	10437993
Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats.	1999 Aug	10445667
Telangiectasia and gingival hyperplasia as side-effects of amlodipine (Norvasc) in a 3-year-old girl.	1999 Jul	10429995
[Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats].	1999 May	10480159
Acute interstitial nephritis induced by crack cocaine binge.	1999 May	10344374
Calcium channel blockers and benign hypertension.	1999 May 10	10326948
Role of nitric oxide in the control of cardiac oxygen consumption in B(2)-kinin receptor knockout mice.	1999 Oct	10523327
Use of ambulatory blood pressure monitoring to evaluate the selective angiotensin II receptor antagonist, telmisartan, and other antihypertensive drugs.	2000	10904241
Amlodipine besylate induced acute interstitial nephritis.	2000 Aug	10940749
Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions.	2000 Feb-Mar	10805063
Results and clinical implications of the CAPARES trial.	2000 Jul	10932030
Restenosis and clinical outcome in patients treated with amlodipine after angioplasty: results from the Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES).	2000 Mar 1	10716459
Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.	2001 Jun	11403364
A pharmacoeconomic evaluation of results from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES) in Norway and Canada.	2002 Jul	12104059
Severity of hypertension affects improved resistance artery endothelial function by angiotensin-converting enzyme inhibition.	2002 May	11973410
Effects of antihypertensive drugs on peritoneal vessels in hypertensive dogs with mild renal insufficiency.	2003	14763026
Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood.	2003 Oct	12969165
Comparative efficacy and safety of nisoldipine extended-release (ER) and amlodipine (CESNA-III study) in African American patients with hypertension.	2003 Sep	12944032
Antiproteinuric efficacy of losartan in comparison with amlodipine in non-diabetic proteinuric renal diseases: a double-blind, randomized clinical trial.	2003 Sep	12937228
Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.	2004 Apr	15127885
Clinic blood pressure responses to two amlodipine salt formulations, adipate and besylate, in adult Korean patients with mild to moderate hypertension: a multicenter, randomized, double-blind, parallel-group, 8-week comparison.	2005 Jun	16117979
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report.	2006 Dec	17285209
The effect of different antihypertensive drugs on cavernous tissue in experimental chronic renal insufficiency.	2006 Jul-Aug	17048199
Effect of stealthy liposomal topotecan plus amlodipine on the multidrug-resistant leukaemia cells in vitro and xenograft in mice.	2006 Jun	16684125
Pharmacoeconomic consequences of amlodipine besylate therapy in patients undergoing PTCA.	2006 Mar	16406672
Beneficial effects of combined benazepril-amlodipine on cardiac nitric oxide, cGMP, and TNF-alpha production after cardiac ischemia.	2006 May	16775501
A novel stealth liposomal topotecan with amlodipine: apoptotic effect is associated with deletion of intracellular Ca2+ by amlodipine thus leading to an enhanced antitumor activity in leukemia.	2006 May 15	16516327
Effect of food on the bioavailability of amlodipine besylate/atorvastatin calcium combination tablet.	2006 Oct	16988211
Incidence and predictors of angioedema in elderly hypertensive patients at high risk for cardiovascular disease: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).	2006 Sep	16957427
Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension.	2007 Apr	17617280
G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in human epidermoid carcinoma A431 cells.	2007 Apr 1	17217918
Results of a comparative, phase III, 12-week, multicenter, prospective, randomized, double-blind assessment of the efficacy and tolerability of a fixed-dose combination of telmisartan and amlodipine versus amlodipine monotherapy in Indian adults with stage II hypertension.	2007 Dec	18201582
Dysgeusia with amlodipine--a case report.	2007 Feb	17274793
Differential effects of dihydropyridine calcium antagonists on doxorubicin-induced nephrotoxicity in rats.	2007 Feb 28	17234320
Fibroblast apoptosis precedes cardiomyocyte mass reduction during left ventricular remodeling in hypertensive rats treated with amlodipine.	2007 Jun	17563544
Antihypertensive efficacy of amlodipine and losartan after two 'missed' doses in patients with mild to moderate essential hypertension.	2007 Nov-Dec	18034989
Antihypertensive efficacy of the oral direct renin inhibitor aliskiren as add-on therapy in patients not responding to amlodipine monotherapy.	2007 Oct	17917501
Comparison of monotherapy versus combination antihypertensive therapy in elderly patients with essential hypertension.	2008 Apr-May	18388088
Improved attainment of blood pressure and cholesterol goals using single-pill amlodipine/atorvastatin in African Americans: the CAPABLE trial.	2008 Jan	18174006
Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects.	2008 Jan	17986525
Synergistic effect of amlodipine and atorvastatin on blood pressure, left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia.	2008 Mar	18389332
Effects of amlodipine, captopril, and bezafibrate on oxidative milieu in rats with fatty liver.	2008 Mar	17710547
Amlodipine inhibits cell proliferation via PKD1-related pathway.	2008 May 2	18298949
Amlodipine improves endothelial function and metabolic parameters in patients with hypertension.	2009 Mar 20	18199500

Patents

Sample Use Guides

In Vivo Use Guide

Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily. Pediatric starting dose: 2.5 mg to 5 mg once daily. Important Limitation: Doses in excess of 5 mg daily have not been studied.

Route of Administration: Oral

In Vitro Use Guide

amlodipine was effective against A. castellanii and B. mandrillaris at 250μM

Name

Type

Language

AMLODIPINE

Official Name

English

CKD-330 COMPONENT AMLODIPINE

Preferred Name

English

AMLODIPINE [VANDF]

Common Name

English

HGP-0904

Code

English

Amlodipine [WHO-DD]

Common Name

English

3-ETHYL 5-METHYL (±)-2-((2-AMINOETHOXY)METHYL)-4-(O-CHLOROPHENYL)-1,4-DIHYDRO-6-METHYL-3,5-PYRIDINEDICARBOXYLATE

Common Name

English

3,5-PYRIDINEDICARBOXYLIC ACID, 2-((2-AMINOETHOXY)METHYL)-4-(2-CHLOROPHENYL)-1,4-DIHYDRO-6-METHYL-, 3-ETHYL 5-METHYL ESTER, (±)-

Common Name

English

AMLODIPINE [MART.]

Common Name

English

AMLODIPINE [ORANGE BOOK]

Common Name

English

HGP0904

Code

English

AMLODIPINE [MI]

Common Name

English

AMLODIPINE [EMA EPAR]

Common Name

English

amlodipine [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

C10BX14