AMLODIPINE BESYLATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C20H25ClN2O5.C6H6O3S
Molecular Weight	567.051
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C2=C(COCCN)NC(C)=C(C2C3=C(Cl)C=CC=C3)C(=O)OC

InChI

InChIKey=ZPBWCRDSRKPIDG-UHFFFAOYSA-N

InChI=1S/C20H25ClN2O5.C6H6O3S/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;7-10(8,9)6-4-2-1-3-5-6/h5-8,17,23H,4,9-11,22H2,1-3H3;1-5H,(H,7,8,9)

HIDE SMILES / InChI

Molecular Formula	C20H25ClN2O5
Molecular Weight	408.876
Charge	0
Count

Stereochemistry	RACEMIC
Additional Stereochemistry	No
Defined Stereocenters	0 / 1
E/Z Centers	0
Optical Activity	( + / - )

Molecular Formula	C6H6O3S
Molecular Weight	158.175
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 2778		57.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Hypertension 567 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/019787s047lbl.pdf	Primary	Approved 8429	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 8429	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
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 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
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
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
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
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 (mean) Overdose Dose: 75 mg Route: oral Route: single Dose: 75 mg Sources: https://pubmed.ncbi.nlm.nih.gov/9220044/	unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 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 (min) 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 n = 1250 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 1250 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
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 n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 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
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 n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 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 n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 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 (mean) 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 n = 231 Health Status: unhealthy Condition: Hypertension, Pregnancy Age Group: adult Sex: F Population Size: 231 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 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
MRP4 204 CYP1A1 110 CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C19 1478 CYP2E1 882 CYP3A5 73 CYP2C8 911 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 BSEP 402 MRP2 383 MRP3 157	CYP3A 191 CYP2B6 664 CYP3A5 395 P-gp 1537

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22200670/	moderate [IC50 11.3 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP3 207	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23956101/	no [IC50 >133 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	no
CYP1A1 218	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	strong [Ki 0.13 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/\| https://pubmed.ncbi.nlm.nih.gov/17101742/	strong [Ki 1.95 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	strong
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/ \| https://pubmed.ncbi.nlm.nih.gov/10640508/	weak [IC50 57 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	weak
CYP2A6 739	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	weak
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10805063/	weak
CYP3A4 1925	inhibitor 3277 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 1650	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11145223/, https://go.drugbank.com/drugs/DB00381	yes [IC50 22 uM]
CYP2C8 965	inhibitor 3277 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 803	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
OATP1B3 715	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/23571415/	yes
CYP3A5 130	inhibitor 3277 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 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22909231/, https://go.drugbank.com/drugs/DB00381	likely
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210045Orig1s000ClinPharmR.pdf#page=8 Page: (Label) 8	major
CYP3A 191	substrate 3367 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 395	substrate 3367 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 1537	substrate 3367 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 1647	inhibitor 1626 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
Selleck Chemicals	Amlodipine(Norvasc)	http://www.selleckchem.com/products/Amlodipine(Norvasc).html
eMolecules	901374	https://www.emolecules.com/cgi-bin/more?vid=901374

PubMed

Title	Date	PubMed
A double-blind evaluation of the effect of amlodipine on ambulatory blood pressure.	1991	1839434
24-hour blood pressure control with the once-daily calcium antagonist amlodipine.	1991	16296698
The unique binding properties of amlodipine: a long-acting calcium antagonist.	1991 Aug	1834847
A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension.	1992 Oct	1418836
Effects of amlodipine on myocardial infarction, infarct expansion, and ventricular geometry in the rat.	1992 Sep	1387506
Effects of antihypertensive drugs on peritoneal vessels in hypertensive dogs with mild renal insufficiency.	2003	14763026
Biochemical changes on the cardioprotective effect of nicorandil and amlodipine during experimental myocardial infarction in rats.	2003 Dec	14527820
Heterogeneous effect of calcium antagonists on leg oedema: a comparison of amlodipine versus lercanidipine in hypertensive patients.	2003 Oct	14508205
Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients.	2003 Oct	13679494
Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood.	2003 Oct	12969165
Synergistic effect of nicorandil and amlodipine on lysosomal hydrolases during experimental myocardial infarction in rats.	2003 Sep	14499179
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
Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy.	2004	15513305
Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy.	2004	15101793
Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats.	2004 Apr	15127885
Acute renal failure and hepatotoxicity associated with roxithromycin.	2004 Apr	14766998
Effect of slow-release indapamide and perindopril compared with amlodipine on 24-hour blood pressure and left ventricular mass in hypertensive patients of African ancestry.	2004 May	15110902
Effects of valsartan/hydrochlorothiazide and amlodipine on ambulatory blood pressure and plasma norepinephrine levels in high-risk hypertensive patients.	2004 May-Jun	15509131
Comparison of antihypertensive effects of an angiotensin-converting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy.	2005 Apr	15775795
Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine.	2005 Aug	16392774
Exercise-related syncope induced by vasodilator therapy in an elderly hypertensive patient.	2005 Feb	15673366
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
Efficacy and tolerability of combination therapy with valsartan plus hydrochlorothiazide compared with amlodipine monotherapy in hypertensive patients with other cardiovascular risk factors: the VAST study.	2005 May	15978306
An economic evaluation of the 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of mild-to-moderate hypertension in Greece.	2005 Sep	16182115
Indapamide sustained release: a review of its use in the treatment of hypertension.	2006	16451099
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

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:59:59 GMT 2023` Edited by `admin` on `Fri Dec 15 18:59:59 GMT 2023`
Record UNII	864V2Q084H
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

AMLODIPINE BESYLATE

Official Name

English

IMPRIDA-HCT COMPONENT AMLODIPINE BESILATE

Brand Name

English

IMPRIDA COMPONENT AMLODIPINE BESILATE

Brand Name

English

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

Common Name

English

NORVASC

Brand Name

English

AMLODIPINE BESYLATE [ORANGE BOOK]

Common Name

English

AMLODIPINE BENZENESULFONATE [MI]

Common Name

English

AMLODIPINE BESYLATE [EMA EPAR VETERINARY]

Common Name

English

AMLODIPINE BESYLATE COMPONENT OF ONDUARP

Brand Name

English

AMLODIPINE BESILATE COMPONENT OF DAFIRO-HCT

Brand Name

English

DAFIRO COMPONENT AMLODIPINE BESILATE

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF AMTURNIDE

Common Name

English

EXFORGE HCT COMPONENT AMLODIPINE BESYLATE

Common Name

English

AMLODIPINE BESYLATE [USP-RS]

Common Name

English

AMLODIPINE BESYLATE [VANDF]

Common Name

English

3-ETHYL 5-METHYL 2-(2-AMINOETHOXYMETHYL)-4-(2-CHLOROPHENYL)-1,4-DIHYDRO-6-METHYLPYRIDINE-3,5-DICARBOXYLATE MONOBENZENESULPHONATE

Systematic Name

English

AMTURNIDE COMPONENT AMLODIPINE BESYLATE

Common Name

English

AMLODIPINE BESYLATE COMPONENT OF TEKAMLO

Common Name

English

AMLODIPINE (AS BESILATE)

Common Name

English

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

Common Name

English

EXFORGE COMPONENT AMLODIPINE BESYLATE

Brand Name

English

AMLODIPINE BESILATE

Common Name

English

LODIPRESSIN

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF AZOR

Common Name

English

AMLODIPINE BESILATE COMPONENT OF EXFORGE

Brand Name

English

NORLIQVA

Brand Name

English

CONSENSI COMPONENT AMLODIPINE BESYLATE

Brand Name

English

AZOR COMPONENT AMLODIPINE BESYLATE

Common Name

English

UK-48,340-26

Code

English

TWYNSTA COMPONENT AMLODIPINE BESYLATE

Common Name

English

AMLODIPINE BESYLATE COMPONENT OF TRIBENZOR

Brand Name

English

AMLODIPINE BESILATE [MART.]

Common Name

English

AMLESSA COMPONENT AMLODIPINE BESYLATE

Common Name

English

ANTACAL

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF TWYNSTA

Common Name

English

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

Common Name

English

AMLODIPINE BESYLATE [USP IMPURITY]

Common Name

English

TEKAMLO COMPONENT AMLODIPINE BESYLATE

Common Name

English

AMLODIPINE BESILATE COMPONENT OF EXFORGE-HCT

Brand Name

English

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

Common Name

English

AMLODIPINE BESYLATE [USP MONOGRAPH]

Common Name

English

EXFORGE COMPONENT AMLODIPINE BESILATE

Brand Name

English

AMLODIPINE BESYLATE [USAN]

Common Name

English

COPALIA COMPONENT AMLODIPINE BESYLATE

Brand Name

English

EXFORGE-HCT COMPONENT AMLODIPINE BESILATE

Brand Name

English

CADUET COMPONENT AMLODIPINE BESYLATE

Brand Name

English

ONDUARP COMPONENT AMLODIPINE BESYLATE

Brand Name

English

AMLODIPINE BESYLATE [EMA EPAR]

Common Name

English

AMLOR

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF CONSENSI

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF COPALIA

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF EXFORGE HCT

Common Name

English

MONOPINA

Brand Name

English

AMLODIPINE BESYLATE COMPONENT OF CADUET

Brand Name

English

DAFIRO-HCT COMPONENT AMLODIPINE BESILATE

Brand Name

English

TRIBENZOR COMPONENT AMLODIPINE BESYLATE

Brand Name

English

AMLODIPINE BESILATE [JAN]

Common Name

English

LOTREL COMPONENT AMLODIPINE BESYLATE

Common Name

English

NSC-758922

Code

English

Amlodipine besilate [WHO-DD]

Common Name

English

AMLODIPINE BESYLATE COMPONENT OF LOTREL

Common Name

English

AMLODIPINE BESYLATE COMPONENT OF EXFORGE

Brand Name

English

AMLODIPINE BESILATE [EP MONOGRAPH]

Common Name

English

AMLODIPINE BESILATE COMPONENT OF IMPRIDA-HCT

Brand Name

English

AMLODIPINE BESYLATE [HSDB]

Common Name

English

AMLODIPINE BESILATE COMPONENT OF DAFIRO

Brand Name

English

UK-48340-26

Code

English

ISTIN

Brand Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

DAFIRO (AUTHORIZED: HYPERTENSION)