Fimasartan is a non-peptide

angiotensin II receptor antagonist Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

(ARB) used for the treatment of

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 ...

and

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

. Through oral administration, fimasartan blocks

angiotensin II receptor type 1 Angiotensin II receptor type 1 (AT1) is the best characterized angiotensin receptor. It is encoded in humans by the ''AGTR1'' gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pr ...

(AT₁ receptors), reducing pro-hypertensive actions of

angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adre ...

, such as systemic vasoconstriction and water retention by the kidneys. Concurrent administration of fimasartan with diuretic

hydrochlorothiazide Hydrochlorothiazide is a diuretic medication often used to treat high blood pressure and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and to decrease the risk of kidney stones in tho ...

has shown to be safe in clinical trials. Fimasartan was approved for use in South Korea on September 9, 2010, and is available under the brand name Kanarb through Boryung Pharmaceuticals, who are presently seeking worldwide partnership.

Mechanism of action

Fimasartan acts on the kidney's rennin-angiotensin cascade, which begins when

renin Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

release from the kidney causes the breakdown of

angiotensinogen Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adren ...

into

angiotensin I Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the a ...

Angiotensin-converting enzyme Angiotensin-converting enzyme (), or ACE, is a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasoconstr ...

(ACE) then catalyzes the reaction that forms

, which acts on AT₁ receptors on the blood vessels, heart, and kidneys. On blood vessels, the AT₁ receptor is coupled to an intracellular pathway that causes smooth muscle contraction (vasoconstriction) of blood vessels. In blocking the AT₁ receptor, fimasartan inhibits

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vessel ...

, favouring

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstriction, ...

. At the kidney and adrenal gland, AT₁ blockage and prevention of

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a c ...

formation increase excretion of water and salt by the kidneys, which decreases overall

blood volume Blood volume (volemia) is the volume of blood (blood cells and plasma) in the circulatory system of any individual. Humans A typical adult has a blood volume of approximately 5 liters, with females and males having approximately the same blood per ...

. At the heart, AT₁ blockage decreases contractility and the stimulatory effects of the sympathetic nervous system. Collectively, fimasartain leads to a reduction in

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

and alleviation of hypertensive symptoms. ARBs like fimasartan have also shown to be protective against

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

, and

. Fimasartan has been shown to reduce cardiac hypertrophy, fibrosis, remodelling, and unnecessary cell proliferation via blockage of AT₁ activation conceivably through decreased

Endothelin 1 Endothelin 1 (ET-1), also known as preproendothelin-1 (PPET1), is a potent vasoconstrictor peptide produced by vascular endothelial cells. The protein encoded by this gene ''EDN1'' is proteolytically processed to release endothelin 1. Endotheli ...

production, a result of AT1 activation. Fimastartan can also block TGF-β1 production (also AT₁ dependent), which contributes to fibrosis and ventricular damage post-infarct. After ARB administration, mice showed improved prognosis after a myocardial infarction, though further studies still need to be done to assess fimasartan's specific effects on decreasing cardiovascular damage.

Side effects

Side effects In clinical trials, fimasartan was well tolerated in all patients. However, higher dosing (360 mg/day) was accompanied by increased dizziness (most likely due to the momentary decrease in blood pressure) and headaches in a low number of patients. Other side effects such as diarrhea, syncope, and cold feet were also experienced in a low number of subjects, which all resolved without medical intervention.

Pharmacology

Fimasartan is rapidly absorbed and has minimal accumulation in the body 7 days after administration. Fimasartan possesses a

half-life Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...

of 9 to 16 hours, appropriate for daily dosing. Fimasartan was found to be effective in fasted or fed states, with a variety of dosing regimens. In trials, the maximum effects of the drug occurred slightly after the maximum plasma concentration (

T-max T-Max (), stylized T-MAX or T.max, was a South Korean pop music group formed in 2007 under the label 2Step Entertainment (later Planet 905). The group began as a trio, where the "T" in its name was derived from the words "triple" and "trinity". ...

) was achieved, which occurs 30 minutes to 3 hours after dosing. Fimasartan was found mostly in unmetabolized form in the plasma and in

bile Bile (from Latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver (liver bile ...

excretions. Urinary elimination of the drug was low, at less than 3% 24 hours after administration, entailing that the fimasartan does not undergo renal excretion.

Society and culture

Brand names

The drug is also available in Russia as ''Канарб'' (Kanarb). Fimasartan is being marketed in India under the brand name of ''Fimanta'' and ''Fimagen'' through Ajanta Pharma Ltd.

References

{{Angiotensin receptor modulators Angiotensin II receptor antagonists Thioamides