ベシル酸アムロジピン

関: amlodipine、amlodipine besilate、amlodipine maleate

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/12 05:34:07」(JST)

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Amlodipine (as besylate, mesylate or maleate) is a medication used to lower blood pressure and prevent chest pain. It belongs to a group of medications known as dihydropyridine-type calcium channel blockers.^[1]^[2] By widening of blood vessels it lowers blood pressure. In angina, amlodipine increases blood flow to the heart muscle to relieve pain due to angina. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.^[3]

Medical uses

Amlodipine is used in the management of hypertension^[4] and coronary artery disease.

Contraindications

Breastfeeding
Cardiogenic shock
Unstable angina
Systolic and diastolic blood pressure below 90/60 mmHg
Aortic stenosis

Adverse effects

Adverse side effects of the use of amlodipine may include:^[5]

Common: peripheral edema and fatigue
Uncommon: blood disorders, development of breasts in men (gynecomastia), impotence, depression, insomnia, tachycardia, or gingival enlargement
Rarely: erratic behavior, hepatitis, jaundice

Mechanism

Amlodipine inhibits calcium ions into vascular smooth muscle cells and cardiac muscle cells. 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 smooth muscle cells. Negative inotropic effects can be detected in vitro, but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure. As a calcium channel blocker, amlodipine is expected to inhibit the currents of L-type Cav1.3 channels in the zona glomerulosa.^[6] ^[7]

The mechanisms by which amlodipine relieves angina include:

Stable angina: amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, thereby lowering myocardial oxygen demand, at any given level of exercise.^[8]

Prinzmetal's angina: amlodipine blocks spasm of the coronary arteries and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.^[9]

Metabolism

Amlodipine has been studied in healthy volunteers following oral administration of ¹⁴C-labelled drug.^[10] amlodipine is well absorbed by the oral route with a mean oral bioavailability around 60%. It is metabolized in the liver to inactive metabolites via CYP3A4. The half-life of amlodipine is about 30–50 hours, and steady-state plasma concentrations are achieved after 7 to 8 days of daily dosing. Renal elimination is the major route of excretion with about 60% of an administered dose recovered in urine, largely as inactive pyridine metabolites. However, renal impairment does not significantly influence amlodipine elimination.^[11]

Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study

The "Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy" (CASTLE) Study gave the result that both the cheap generic Amlodipine and the more expensive Candesartan cilexetil were both effective in the treatment of mild hypertension stage-1 (maximum 160/100 mm Hg) with no significant difference. Amlodipine decreased systolic and diastolic BP by -15.4/-11.3 mm Hg, while Candesartan cilexetil did so by -15.2/-10.2 mm Hg. But the most common side effect was Peripheral edema, which happened with greater frequency using Amlodipine (22.1%; mild 8.7%, moderate 11.8%, and severe 1.6%), while the increase using Candesartan cilexetil was 8.9%; (mild 8.1%, and moderate 0.8%).^[12]

Combination therapy

If monotherapy with Amlodipine or Candesartan is not sufficient to reach the reducing blood pressure target, a combination of Amlodipine 5mg and Candesartan 8mg can be effective, lowering blood pressure after 12 weeks in patients not adequately controlled by monotherapy.^[13]

History

Pfizer's patent protection on Norvasc lasted until 2007; total patent expiration occurred later in 2007.^[14] A number of generic versions are available. In the United Kingdom, tablets of amlodipine from different suppliers may contain different salts. The strength of the tablets is expressed in terms of amlodipine base, i.e., without the salts. Tablets containing different salts are therefore considered interchangeable.The efficacy and tolerability of a fixed-dose combination of amlodipine 5 mg and perindopril 4 mg, an angiotensin converting enzyme inhibitor, have recently been confirmed in a prospective, observational, multicentre trial of 1250 hypertensive patients.^[15]

References

^ "Amlodipine: MedlinePlus Drug Information". www.nlm.nih.gov. Retrieved 2015-05-21.
^ Cash, Jill C.; Glass, Cheryl Anne (2014-02-10). Family Practice Guidelines, Third Edition. Springer Publishing Company. ISBN 9780826197825.
^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
^ Wang, JG (2009). "A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention". Vascular health and risk management 5: 593–605. doi:10.2147/vhrm.s6203. PMID 19688100.
^ Munoz, Ricardo; Vetterly, Carol G.; Roth, Stephen J.; Cruz, Eduardo da (2007-10-18). Handbook of Pediatric Cardiovascular Drugs. Springer Science & Business Media. ISBN 9781846289538.
^ Arcangelo, Virginia Poole; Peterson, Andrew M. (2006). Pharmacotherapeutics for Advanced Practice: A Practical Approach. Lippincott Williams & Wilkins. ISBN 9780781757843.
^ Ritter, James; Lewis, Lionel; Mant, Timothy; Ferro, Albert (2012-12-11). A Textbook of Clinical Pharmacology and Therapeutics, 5Ed. CRC Press. ISBN 9781444113006.
^ Li, Y. Robert (2015-04-06). Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based Therapeutics. John Wiley & Sons. ISBN 9780470915370.
^ LEARNING, JONES & BARTLETT; Bartlett, Jones and (2012-07-15). 2013 Nurse's Drug Handbook. Jones & Bartlett Publishers. ISBN 9781449642846.
^ Beresford AP, McGibney D, Humphrey MJ, Macrae PV, Stopher DA (February 1988). "Metabolism and kinetics of amlodipine in man". Xenobiotica 18 (2): 245–54. doi:10.3109/00498258809041660. PMID 2967593.
^ Brittain, Harry G. (2012-05-09). Profiles of Drug Substances, Excipients and Related Methodology. Academic Press. ISBN 9780123977564.
^ AM J Cardiol. "Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators". Retrieved June 22, 2015.
^ Kazuaki Nishio, Takeshi Kondo, Youichi Kobayashi. "Efficacy and Tolerability of Candesartan Cilexetil and Amlodipine in Patients with Poorly Controlled Essential Hypertension". Retrieved July 21, 2015.
^ Kennedy VB (22 March 2007). "Pfizer loses court ruling on Norvasc patent". MarketWatch.
^ Bahl VK, Jadhav UM, Thacker HP (2009). "Management of hypertension with the fixed combination of perindopril and amlodipine in daily clinical practice: results from the STRONG prospective, observational, multicenter study". Am J Cardiovasc Drugs 9 (3): 135–42. doi:10.2165/00129784-200909030-00001. PMID 19463019.

External links

U.S. National Library of Medicine: Drug Information Portal - Amlodipine

UpToDate Contents

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1. Choice of drug therapy in primary (essential) hypertension
2. 収縮機能障害による心不全におけるカルシウム拮抗剤 calcium channel blockers in heart failure due to systolic dysfunction
3. 安定狭心症のマネージメントにおけるカルシウム拮抗剤 calcium channel blockers in the management of stable angina pectoris
4. カルシウム拮抗剤の主な副作用および安全性 major side effects and safety of calcium channel blockers
5. Pharmacologic therapy of heart failure with reduced ejection fraction

English Journal

New methods for amlodipine and valsartan native spectrofluorimetric determination, with factors optimization study.

El-Kosasy AM1, Tawakkol SM2, Ayad MF1, Sheta AI3.
Talanta.Talanta.2015 Oct 1;143:402-13. doi: 10.1016/j.talanta.2015.05.012. Epub 2015 May 12.
Four native fluorescence methods were suggested for simultaneous determination of amlodipine (AML) and valsartan (VAL). These methods were based on excitation of both drugs at λex 300nm, in one step, to give maximum emission at λem 378 and 496nm for AML and VAL, respectively. The first method, sin
PMID 26078177

An approach to the determination of the enantiomeric excess at the extreme case by capillary electrophoresis.

Xiao H1, Fu X1, Liang S1, Li Y2, Bao JJ3, Zhang Y4.
Journal of chromatography. A.J Chromatogr A.2015 Aug 21;1408:250-254. doi: 10.1016/j.chroma.2015.07.006. Epub 2015 Jul 4.
Capillary electrophoresis (CE) has been applied to determine the percentage of enantiomeric excess (ee%) of chiral compounds. In such assays, the quality of chiral selectors (CSs) plays vital roles in resolving the enantiomers for accurate determination of the ee%. Selecting an efficient CS is usual
PMID 26166294

Treatment of Hypertensive Patients With Diabetes and Microalbuminuria With Combination Indapamide SR/Amlodipine: Retrospective Analysis of NESTOR.

Hanon O1, Boully C2, Caillard L2, Labourée F2, Cochiello S2, Chaussade E2.
American journal of hypertension.Am J Hypertens.2015 Aug;28(8):1064-71. doi: 10.1093/ajh/hpu297. Epub 2015 Jan 26.
BACKGROUND: Combination treatments for hypertension most often include a renin-angiotensin-aldosterone system (RAAS) inhibitor. However, systolic blood pressure (SBP) remains difficult to control. Non-RAAS-inhibiting strategies such as calcium channel blocker/thiazide-like diuretic combinations may
PMID 25628416

Japanese Journal

降圧配合錠の製剤学的性質が成分溶出性に与える影響

分析化学 64(11), 835-844, 2015
NAID 130005129314

透析導入時の薬剤選択に苦慮した急性間欠性ポルフィリン症の1例

日本透析医学会雑誌 48(7), 437-441, 2015
NAID 130005090710

アムロジピンベシル酸塩製剤と酸化マグネシウム製剤の‌同時簡易懸濁による主薬量の変動

医療薬学 40(4), 252-257, 2014
NAID 130005062834

「besylate」

Amlodipine
Systematic (IUPAC) name
	(RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
Clinical data
Trade names	Norvasc
AHFS/Drugs.com	monograph
MedlinePlus	a692044
Licence data	US FDA:link
Pregnancy; category	AU: C; US: C (Risk not ruled out);
Legal status	UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral (tablets)
Pharmacokinetic data
Bioavailability	64 to 90%
Metabolism	Hepatic
Biological half-life	30 to 50 hours
Excretion	Renal
Identifiers
CAS Registry Number	88150-42-9
ATC code	C08CA01
PubChem	CID: 2162
IUPHAR/BPS	6981
DrugBank	DB00381
ChemSpider	2077
UNII	1J444QC288
KEGG	D07450
ChEBI	CHEBI:2668
ChEMBL	CHEMBL1491
Chemical data
Formula	C20H25ClN2O5
Molecular mass	408.879 g/mol
	SMILES Clc1ccccc1C2C(=C(/N/C(=C2/C(=O)OCC)COCCN)C)\C(=O)OC ;
	InChI 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 ; Key:HTIQEAQVCYTUBX-UHFFFAOYSA-N ;
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ベシル酸、ベシレート、(化合物)シル酸塩

関: besilate

[1] "Amlodipine: MedlinePlus Drug Information". www.nlm.nih.gov. Retrieved 2015-05-21.

[2] Cash, Jill C.; Glass, Cheryl Anne (2014-02-10). Family Practice Guidelines, Third Edition. Springer Publishing Company. ISBN 9780826197825.

[3] "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.

[4] Wang, JG (2009). "A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention". Vascular health and risk management 5: 593–605. doi:10.2147/vhrm.s6203. PMID 19688100.

[5] Munoz, Ricardo; Vetterly, Carol G.; Roth, Stephen J.; Cruz, Eduardo da (2007-10-18). Handbook of Pediatric Cardiovascular Drugs. Springer Science & Business Media. ISBN 9781846289538.

[6] Arcangelo, Virginia Poole; Peterson, Andrew M. (2006). Pharmacotherapeutics for Advanced Practice: A Practical Approach. Lippincott Williams & Wilkins. ISBN 9780781757843.

[7] Ritter, James; Lewis, Lionel; Mant, Timothy; Ferro, Albert (2012-12-11). A Textbook of Clinical Pharmacology and Therapeutics, 5Ed. CRC Press. ISBN 9781444113006.

[8] Li, Y. Robert (2015-04-06). Cardiovascular Diseases: From Molecular Pharmacology to Evidence-Based Therapeutics. John Wiley & Sons. ISBN 9780470915370.

[9] LEARNING, JONES & BARTLETT; Bartlett, Jones and (2012-07-15). 2013 Nurse's Drug Handbook. Jones & Bartlett Publishers. ISBN 9781449642846.

[pmid2967593-10] Beresford AP, McGibney D, Humphrey MJ, Macrae PV, Stopher DA (February 1988). "Metabolism and kinetics of amlodipine in man". Xenobiotica 18 (2): 245–54. doi:10.3109/00498258809041660. PMID 2967593.

[11] Brittain, Harry G. (2012-05-09). Profiles of Drug Substances, Excipients and Related Methodology. Academic Press. ISBN 9780123977564.

[12] AM J Cardiol. "Comparative effects of candesartan cilexetil and amlodipine in patients with mild systemic hypertension. Comparison of Candesartan and Amlodipine for Safety, Tolerability and Efficacy (CASTLE) Study Investigators". Retrieved June 22, 2015.

[13] Kazuaki Nishio, Takeshi Kondo, Youichi Kobayashi. "Efficacy and Tolerability of Candesartan Cilexetil and Amlodipine in Patients with Poorly Controlled Essential Hypertension". Retrieved July 21, 2015.

[14] Kennedy VB (22 March 2007). "Pfizer loses court ruling on Norvasc patent". MarketWatch.

[test-15] Bahl VK, Jadhav UM, Thacker HP (2009). "Management of hypertension with the fixed combination of perindopril and amlodipine in daily clinical practice: results from the STRONG prospective, observational, multicenter study". Am J Cardiovasc Drugs 9 (3): 135–42. doi:10.2165/00129784-200909030-00001. PMID 19463019.

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案内

案内

amlodipine besylate