Details
| Stereochemistry | RACEMIC |
| Molecular Formula | C20H25ClN2O5.ClH |
| Molecular Weight | 445.337 |
| Optical Activity | ( + / - ) |
| Defined Stereocenters | 0 / 1 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CCOC(=O)C1=C(COCCN)NC(C)=C(C1C2=C(Cl)C=CC=C2)C(=O)OC
InChI
InChIKey=BSBOZVBRVBLCLO-UHFFFAOYSA-N
InChI=1S/C20H25ClN2O5.ClH/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;1H
| 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 | ClH |
| Molecular Weight | 36.461 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
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.
Originator
Sources: http://www.drugfuture.com/chemdata/amlodipine.html | http://www.pfizer.com/about/history/all
Curator's Comment: # Pfizer
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 57.0 nM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | NORVASC Approved UseAmlodipine 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 Date1992 |
|||
| Primary | NORVASC Approved UseAmlodipine 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 Date1992 |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | 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 |
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 |
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 |
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 | Co-administered | 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 |
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 |
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 |
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 |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
48 h |
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 |
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 |
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 |
Funbound
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
2% |
AMLODIPINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
Disc. AE: Sinus tachycardia, Metabolic acidosis... AEs leading to discontinuation/dose reduction: Sinus tachycardia (1 patient) Sources: Metabolic acidosis (1 patient) Hypocalcemia (1 patient) |
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: |
unhealthy, adult n = 1250 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 1250 Sources: |
Disc. AE: Headache... AEs leading to discontinuation/dose reduction: Headache (1.5%) Sources: |
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: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
DLT: Edema, Dizziness... Dose limiting toxicities: Edema (10.8%) Sources: Dizziness (3.4%) Flushing (2.6%) Palpitation (4.5%) |
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: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
DLT: Edema, Dizziness... Dose limiting toxicities: Edema (1.8%) Sources: Dizziness (1.1%) Flushing (0.7%) Palpitation (0.7%) |
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: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
DLT: Edema, Dizziness... Dose limiting toxicities: Edema (3%) Sources: Dizziness (3.4%) Flushing (1.4%) Palpitation (1.4%) |
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: |
unhealthy, adult n = 231 Health Status: unhealthy Condition: Hypertension, Pregnancy Age Group: adult Sex: F Population Size: 231 Sources: |
Other AEs: Neonatal disorder NOS... |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Hypocalcemia | 1 patient Disc. AE |
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
| Metabolic acidosis | 1 patient Disc. AE |
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
| Sinus tachycardia | 1 patient Disc. AE |
75 mg single, oral (mean) Overdose |
unhealthy, 42 years n = 1 Health Status: unhealthy Condition: Hypertension Age Group: 42 years Sex: F Population Size: 1 Sources: |
| Headache | 1.5% Disc. AE |
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: |
unhealthy, adult n = 1250 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 1250 Sources: |
| Edema | 10.8% DLT |
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: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Flushing | 2.6% DLT |
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: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Dizziness | 3.4% DLT |
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: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Palpitation | 4.5% DLT |
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: |
unhealthy, adult n = 268 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 268 Sources: |
| Flushing | 0.7% DLT |
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: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Palpitation | 0.7% DLT |
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: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Dizziness | 1.1% DLT |
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: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Edema | 1.8% DLT |
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: |
unhealthy, adult n = 275 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 275 Sources: |
| Flushing | 1.4% DLT |
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: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Palpitation | 1.4% DLT |
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: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Edema | 3% DLT |
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: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Dizziness | 3.4% DLT |
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: |
unhealthy, adult n = 296 Health Status: unhealthy Condition: Hypertension Age Group: adult Sex: unknown Population Size: 296 Sources: |
| Neonatal disorder NOS | 11 patient | 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: |
unhealthy, adult n = 231 Health Status: unhealthy Condition: Hypertension, Pregnancy Age Group: adult Sex: F Population Size: 231 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| moderate [IC50 11.3 uM] | ||||
| no [IC50 >133 uM] | ||||
| no [IC50 >133 uM] | ||||
| no [IC50 >133 uM] | ||||
| no [IC50 >133 uM] | ||||
| no | ||||
| strong [Ki 0.13 uM] | ||||
| strong [Ki 1.95 uM] | ||||
| strong | ||||
| weak [IC50 57 uM] | ||||
| weak | ||||
| weak | ||||
| weak | ||||
| 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. Page: (Label 2) 24 |
|||
| yes [IC50 22 uM] | ||||
| yes [Inhibition 2 uM] | ||||
| yes | ||||
| yes | ||||
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. Page: (Label 2) 24 |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| likely | ||||
| major | ||||
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 |
||
| 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 CYP3A5*1/*3 polymorphism exhibited the highest change in blood pressure, followed by CYP3A5*4, CYP3A5*1/*1, and CYP3A5*6 |
|||
| yes | yes (pharmacogenomic study) Comment: Amlodipine pharmacokinetics was affected by the genetic polymorphisms of the ABCB1 gene in humans. |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| 24-hour blood pressure control with the once-daily calcium antagonist amlodipine. | 1991 |
|
| A randomized, placebo-controlled, double-blind comparison of amlodipine and atenolol in patients with essential hypertension. | 1992 Oct |
|
| Pharmacologic characterization of FR172516: a new combined calcium channel-blocking and beta-adrenoceptor-blocking agent. | 1999 Apr |
|
| Amlodipine treatment of cocaine dependence. | 1999 Apr-Jun |
|
| Effects of amlodipine on nitric oxide synthase mRNA expression and coronary microcirculation in prolonged nitric oxide blockade-induced hypertensive rats. | 1999 Aug |
|
| Telangiectasia and gingival hyperplasia as side-effects of amlodipine (Norvasc) in a 3-year-old girl. | 1999 Jul |
|
| [Effects of benidipine hydrochloride (Coniel) on blood pressure, heart rate and plasma norepinephrine concentration in spontaneously hypertensive rats]. | 1999 May |
|
| Acute interstitial nephritis induced by crack cocaine binge. | 1999 May |
|
| Calcium channel blockers and benign hypertension. | 1999 May 10 |
|
| Role of nitric oxide in the control of cardiac oxygen consumption in B(2)-kinin receptor knockout mice. | 1999 Oct |
|
| [Effects of calcium antagonists on atherosclerosis progression and intima media thickness]. | 2000 |
|
| Use of ambulatory blood pressure monitoring to evaluate the selective angiotensin II receptor antagonist, telmisartan, and other antihypertensive drugs. | 2000 |
|
| Amlodipine besylate induced acute interstitial nephritis. | 2000 Aug |
|
| Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers. | 2000 Feb |
|
| Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. | 2000 Feb-Mar |
|
| Results and clinical implications of the CAPARES trial. | 2000 Jul |
|
| Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. | 2000 Nov |
|
| Differential effect of chronic inhibition of calcium channel and angiotensin II type 1-receptor on aldosterone synthesis in spontaneously hypertensive rats. | 2000 Oct |
|
| Haemodynamic and metabolic effects of rilmenidine in hypertensive patients with metabolic syndrome X. A double-blind parallel study versus amlodipine. | 2000 Oct |
|
| Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses. | 2001 Feb |
|
| Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. | 2001 Jun |
|
| Mechanisms of plaque stabilization for the dihydropyridine calcium channel blocker amlodipine: review of the evidence. | 2002 Dec |
|
| [Amlodipine-induced acute hepatitis]. | 2002 Jun-Jul |
|
| Tolerability of long-term treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives. | 2002 Nov |
|
| Effects of antihypertensive drugs on peritoneal vessels in hypertensive dogs with mild renal insufficiency. | 2003 |
|
| Dysphonia secondary to perindopril treatment. | 2003 Apr |
|
| Arterial hypertension with brachydactyly in a 15-year-old boy. | 2003 Aug |
|
| Amlodipine and carvedilol prevent cytotoxicity in cortical neurons isolated from stroke-prone spontaneously hypertensive rats. | 2004 Apr |
|
| Acute renal failure and hepatotoxicity associated with roxithromycin. | 2004 Apr |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
| Indapamide sustained release: a review of its use in the treatment of hypertension. | 2006 |
|
| Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report. | 2006 Dec |
|
| Effect of stealthy liposomal topotecan plus amlodipine on the multidrug-resistant leukaemia cells in vitro and xenograft in mice. | 2006 Jun |
|
| Pharmacoeconomic consequences of amlodipine besylate therapy in patients undergoing PTCA. | 2006 Mar |
|
| 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 |
|
| 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 |
|
| Antihypertensive efficacy of the oral direct renin inhibitor aliskiren as add-on therapy in patients not responding to amlodipine monotherapy. | 2007 Oct |
|
| Comparison of monotherapy versus combination antihypertensive therapy in elderly patients with essential hypertension. | 2008 Apr-May |
|
| Improved attainment of blood pressure and cholesterol goals using single-pill amlodipine/atorvastatin in African Americans: the CAPABLE trial. | 2008 Jan |
|
| Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects. | 2008 Jan |
|
| Synergistic effect of amlodipine and atorvastatin on blood pressure, left ventricular remodeling, and C-reactive protein in hypertensive patients with primary hypercholesterolemia. | 2008 Mar |
|
| Effects of amlodipine, captopril, and bezafibrate on oxidative milieu in rats with fatty liver. | 2008 Mar |
|
| Amlodipine improves endothelial function and metabolic parameters in patients with hypertension. | 2009 Mar 20 |
Sample Use Guides
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
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 18:51:46 GMT 2023
by
admin
on
Fri Dec 15 18:51:46 GMT 2023
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| Record UNII |
96YOS2ZYQI
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| Record Status |
Validated (UNII)
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ENANTIOMER -> RACEMATE | |||
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ENANTIOMER -> RACEMATE |
