Pitavastatin
Encyclopedia
Pitavastatin is a member of the medication
class of statin
s, marketed in the United States under the trade name Livalo. Like other statins, it is an inhibitor of HMG-CoA reductase
, the enzyme
that catalyses the first step of cholesterol
synthesis. It has been available in Japan since 2003, and is being marketed under licence in South Korea
and in India
. It is likely that pitavastatin will be approved for use in hypercholesterolaemia (elevated levels of cholesterol in the blood) and for the prevention of cardiovascular disease
outside South and Southeast Asia as well.
. There have been many studies confirming that pitavastatin can consistently increase HDL cholesterol (10–25%), especially in patients with HDL lower than 40 mg/dl, in addition to strong reducing LDL cholesterol (–40%). As a consequence, pitavastatin is most likely to be appropriate for patients with metabolic syndrome
with high LDL, low HDL and diabetes mellitus
. Another reason is that pitavastatin, unlike other potent statins, does not affect glycelate control of type 2 diabetes mellitus.
cytochrome P450 enzymes, leading to an increased potential for drug interaction
s and problems with certain foods (such as grapefruit
juice). Pitavastatin appears to be a substrate of CYP2C9
, and not CYP3A4
(which is a common source of interactions in other statins). As a result, pitavastatin is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines.
by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo
. Pitavastatin was approved for use in the United States by the FDA on 08/03/2009 under the trade name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK on 17 August 2010.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
class of statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
s, marketed in the United States under the trade name Livalo. Like other statins, it is an inhibitor of HMG-CoA reductase
HMG-CoA reductase
HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids...
, the enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that catalyses the first step of cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
synthesis. It has been available in Japan since 2003, and is being marketed under licence in South Korea
South Korea
The Republic of Korea , , is a sovereign state in East Asia, located on the southern portion of the Korean Peninsula. It is neighbored by the People's Republic of China to the west, Japan to the east, North Korea to the north, and the East China Sea and Republic of China to the south...
and in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
. It is likely that pitavastatin will be approved for use in hypercholesterolaemia (elevated levels of cholesterol in the blood) and for the prevention of cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
outside South and Southeast Asia as well.
Uses
Like the other statins, pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of cardiovascular diseaseCardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
. There have been many studies confirming that pitavastatin can consistently increase HDL cholesterol (10–25%), especially in patients with HDL lower than 40 mg/dl, in addition to strong reducing LDL cholesterol (–40%). As a consequence, pitavastatin is most likely to be appropriate for patients with metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
with high LDL, low HDL and diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
. Another reason is that pitavastatin, unlike other potent statins, does not affect glycelate control of type 2 diabetes mellitus.
Side-effects
Common statin-related side-effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins. However, pitavastatin seems to lead to less muscle side effects than other statins, since coenzyme Q10 is not significantly reduced.Metabolism and interactions
Most statins are metabolised in part by one or more hepaticLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
cytochrome P450 enzymes, leading to an increased potential for drug interaction
Drug interaction
A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. Typically, interaction between drugs come to mind...
s and problems with certain foods (such as grapefruit
Grapefruit
The grapefruit , is a subtropical citrus tree known for its sour fruit, an 18th-century hybrid first bred in Barbados. When found, it was named the "forbidden fruit"; it has also been misidentified with the pomelo or shaddock , one of the parents of this hybrid, the other being sweet orange The...
juice). Pitavastatin appears to be a substrate of CYP2C9
CYP2C9
Cytochrome P450 2C9 is a protein that in humans is encoded by the CYP2C9 gene.- Function :CYP2C9 is an important cytochrome P450 enzyme with a major role in the oxidation of both xenobiotic and endogenous compounds. CYP2C9 makes up about 18% of the cytochrome P450 protein in liver microsomes...
, and not CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
(which is a common source of interactions in other statins). As a result, pitavastatin is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines.
History
Pitavastatin (previously known as itavastatin, itabavastin, nisvastatin, NK-104 or NKS-104) was discovered in JapanJapan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
by Nissan Chemical Industries and developed further by Kowa Pharmaceuticals, Tokyo
Tokyo
, ; officially , is one of the 47 prefectures of Japan. Tokyo is the capital of Japan, the center of the Greater Tokyo Area, and the largest metropolitan area of Japan. It is the seat of the Japanese government and the Imperial Palace, and the home of the Japanese Imperial Family...
. Pitavastatin was approved for use in the United States by the FDA on 08/03/2009 under the trade name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK on 17 August 2010.