Levamlodipine
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Levamlodipine (
INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
), also known as levoamlodipine or S-amlodipine is a pharmacologically active
enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...
of
amlodipine Amlodipine, sold under the brand name Norvasc among others, is a calcium channel blocker medication used to treat high blood pressure and coronary artery disease. It is taken by mouth. Common side effects include swelling, feeling tired, ab ...
. Amlodipine belongs to the dihydropyridine group of
calcium channel blocker Calcium channel blockers (CCB), calcium channel antagonists or calcium antagonists are a group of medications that disrupt the movement of calcium () through calcium channels. Calcium channel blockers are used as antihypertensive drugs, i.e., as ...
used as an
antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Evidence suggests tha ...
and
antianginal An antianginal is a drug used in the treatment of ''angina pectoris'', a symptom of ischaemic heart disease. Examples Drugs used are nitrates, beta blockers, or calcium channel blockers. Nitrates Nitrates cause vasodilation of the venous capaci ...
agent. Levamlodipine is currently marketed in Russia under the brand name EsCordi Cor ( Actavis Pharma), in Brazil under the brand name Novanlo ( Biolab Sanus) and in India under the trade names Eslo (Zuventus Healthcare Ltd.), Asomex ( Emcure Pharmaceutical Ltd.), and Espin (Intas Pharmaceuticals Ltd.). In December 2019 Levamlodipine received US FDA approval under the name "Conjupri".


Mechanism of action

Amlodipine blocks the transmembrane influx of calcium into the vascular and cardiac smooth muscles resulting in vasodilation and hence a fall in blood pressure. Levamlodipine is an allosteric modulator and acts on the L-type of
calcium channels A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, although there are also ligand-gated calcium channels. Comparison tables The following tables ex ...
. Receptor binding studies have shown that out of the two forms only the (''S'')-enantiomer of amlodipine binds to and blocks L-type calcium channels whereas the (''R'')-enantiomer has no activity on these channels. The precise mechanisms by which levamlodipine relieves
angina Angina, also known as angina pectoris, is chest pain or pressure, usually caused by ischemia, insufficient blood flow to the Cardiac muscle, heart muscle (myocardium). It is most commonly a symptom of coronary artery disease. Angina is typical ...
have not been fully explored, but are thought to include the following: * Decreases peripheral resistance by arteriolar vasodilatation leading to the reduction in oxygen requirement and energy consumption of cardiac smooth muscles. * Decreases coronary vascular resistance and can lead to an increase in coronary blood flow.


Pharmacokinetics and metabolism

Administration of levamlodipine (2.5 mg) as a single dose gives maximum plasma concentration ( ''C''max) of 8.3 to 9.3 ng/mL in 2 to 3 hrs (''T''max). It is extensively (about 90%) converted to inactive metabolites via hepatic
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
with 10% of the parent compound and 60% of the metabolites excreted in the urine. Levamlodipine shows approximately 93%
plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...
in hypertensive patients. The mean AUC0–''t'' value (''t'' = 48 hrs) of levamlodipine tablets (2.5 mg) is . The plasma
elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...
of levamlodipine has been found to be .


Clinical experience

Various clinical studies have shown that levamlodipine has more selectivity and better efficacy than (''R'')-amlodipine. In pooled data, from three comparative studies conducted in 200 patients with mild to moderate
hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
, 2.5 mg of levamlodipine was found to be equivalent in its blood pressure lowering efficacy to 5 mg of amlodipine. The average reduction in systolic BP was 19±3 vs 19±4, 20±2 vs 19±3 and 20±2 vs 19±3 mm of Hg recorded in standing, supine and sitting position respectively for levamlodipine compared to racemic amlodipine. The studies also reported a significant reduction in total
cholesterol Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
and
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...
levels with levamlodipine, which was not seen with amlodipine. Efficacy and safety of levamlodipine (2.5 mg, once daily) has been evaluated in the patients with
isolated systolic hypertension In medicine, systolic hypertension is defined as an elevated Blood pressure, systolic blood pressure (SBP). If the systolic blood pressure is elevated (>140) with a normal (<90) diastolic blood pressure (DBP), it is called isolated systolic hypert ...
(ISH). Levamlodipine effectively reduced the systolic BP (mean reduction 22±14 mm of Hg) in all grades of ISH. After 28 days of the treatment, overall responder rate was 73%. It significantly reduced the systolic and diastolic BP within 4 weeks with a responder rate of 96.5%. Elderly hypertensives with
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
exhibits higher response to levamlodipine therapy than non-diabetic patients. Levamlodipine is an effective switch-over option for the elderly patients who experience
oedema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
and other adverse events with racemic amlodipine.


Safety and tolerability

The use of
racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...
amlodipine is commonly associated with adverse events like
peripheral edema Peripheral edema is edema (accumulation of fluid causing swelling) in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body (those hanging distally), it may be called dependent edem ...
and other side effects like headache, dizziness, flushing and abdominal pain. Controlled clinical trials showed that levamlodipine is rarely associated with these side effects. No controlled clinical study of levamlodipine has been performed in patients with hepatic impairment and renal impairment. Clinical studies in patients with normal liver function have shown that there is no elevation in the hepatic enzymes with the use of levamlodipine. However, caution should be taken while administering levamlodipine to such patients. In a
postmarketing surveillance Postmarketing surveillance (PMS), also known as post market surveillance, is the practice of monitoring the safety of a pharmaceutical drug or medical device after it has been released on the market and is an important part of the science of pharmac ...
study, levamlodipine (2.5/5 mg) was found to be well tolerated (''n'' = 1859) in patients with hypertension. Out of 314 patients, who reported peripheral edema with conventional amlodipine were switched over to levamlodipine and edema was resolved in 310 patients (98.72%) at the end of 4 weeks. Only in 4 patients was edema sustained. Only 30 patients (out of 1859) reported side effects. These side effects included
vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...
,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
, cough, headache, fever, mild difficulty in breathing and
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...
. Adverse events were mild in nature and no serious adverse events were reported.


References

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