Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol lowering

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

class of

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

s. Pitavastatin is an inhibitor of

HMG-CoA reductase HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-limiting enzyme (NADH-dependent, ; NADPH-dependent, ) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other ...

, the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that catalyses the first step of

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

synthesis. It was patented in 1987 and approved for medical use in 2003. It is available in Japan,

South Korea South Korea, officially the Republic of Korea (ROK), is a country in East Asia. It constitutes the southern half of the Korea, Korean Peninsula and borders North Korea along the Korean Demilitarized Zone, with the Yellow Sea to the west and t ...

and in

India India, officially the Republic of India, is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area; the List of countries by population (United Nations), most populous country since ...

. In the US, it received FDA approval in 2009. Kowa Pharmaceuticals, a subsidiary of Kowa Company, is the owner of the American patent to pitavastatin.

Medical uses

Pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of

cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...

. A 2009 study of the 104-week LIVES trial found pitavastatin increased

HDL cholesterol High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

, especially in patients with HDL lower than 40 mg/dL, who had a 24.6% rise, in addition to reducing

LDL cholesterol Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall dens ...

31.3%. HDL improved in patients who switched from other statins and rose over time. In the 70-month CIRCLE observational study, pitavastatin increased HDL more than atorvastatin. It has neutral or possibly beneficial effects on glucose control. As a consequence, pitavastatin is likely to be appropriate for patients with

metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...

plus high LDL, low HDL and

diabetes mellitus Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

Side effects

Common statin-related side effects (headaches, stomach upset, abnormal

liver function test Liver function tests (LFTs or LFs), also referred to as a hepatic panel or liver panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial ...

s and muscle cramps) were similar to other statins. Pitavastatin is a lipophilic statin. Reports indicate that this statin may lead to fewer muscle side effects than other statins. One study found that coenzyme Q₁₀ was not reduced as much as with certain other statins (though this is unlikely given the inherent chemistry of the HMG-CoA reductase pathway that all statin drugs inhibit). There is evidence that pitavastatin does not increase insulin resistance in humans, with insulin resistance assessed by the

homeostatic model assessment In biology, homeostasis (British also homoeostasis; ) is the state of steady internal physical and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and includes many variables, s ...

(HOMA-IR) method.

Hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 ...

or increased levels of serum uric acid have been reported with pitavastatin.

Metabolism and interactions

Statins are metabolised in part by one or more

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzymes, leading to an increased potential for

drug interaction In pharmaceutical sciences, drug interactions occur when a drug's mechanism of action is affected by the concomitant administration of substances such as foods, beverages, or other drugs. A popular example of drug–food interaction is the effect ...

s and problems with certain foods (such as

grapefruit The grapefruit (''Citrus'' × ''paradisi'') is a subtropical citrus tree known for its relatively large, sour to semi-sweet, somewhat bitter fruit. The flesh of the fruit is segmented and varies in color from pale yellow to dark red. Grapefru ...

juice). The primary metabolism pathway of pitavastatin is

glucuronidation Glucuronidation is often involved in drug metabolism of substances such as drugs, pollutants, bilirubin, androgens, estrogens, mineralocorticoids, glucocorticoids, fatty acid derivatives, retinoids, and bile acids. These linkages involve gly ...

. It is minimally metabolized by the CYP450 enzymes

CYP2C9 Cytochrome P450 family 2 subfamily C member 9 (abbreviated CYP2C9) is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, t ...

and

CYP2C8 Cytochrome P4502C8 (CYP2C8) is a member of the cytochrome P450 mixed-function oxidase system involved in the metabolism of xenobiotics in the body. Cytochrome P4502C8 also possesses epoxygenase activity, i.e. it metabolizes long-chain polyunsat ...

,. but not by

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

(which is a common source of interactions in other statins). As a result, it 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 Japan by

Nissan Chemical Industries is a Japanese company and constituent of the Nikkei 225 stock index. History The company was founded in 1887 as "Tokyo Jinzo Hiryo" (Tokyo Artificial Fertilizer Company) by Jokichi Takamine, Eiichi Shibusawa and Takashi Masuda. Takamine ser ...

and developed further by Kowa Pharmaceuticals,

Tokyo Tokyo, officially the Tokyo Metropolis, is the capital of Japan, capital and List of cities in Japan, most populous city in Japan. With a population of over 14 million in the city proper in 2023, it is List of largest cities, one of the most ...

. Pitavastatin was approved for use in the United States by the FDA in August 2009, under the brand name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK in August 2010. Zypitamag (pitavastatin magnesium), a pharmaceutical alternative to Livalo, was approved for use in the United States by the FDA in 2017.

Society and culture

Brand names

Pitavastatin is marketed in the United States under the brand names Livalo and Zypitamag, and in the European Union and Russia under the brand name Livazo.

References

{{Statins Statins Quinolines Diols Carboxylic acids 4-Fluorophenyl compounds Cyclopropyl compounds Beta hydroxy acids Drugs developed by Eli Lilly and Company