Pravastatin

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Pravastatin
Pravastatin.svg
Clinical data
Trade names Pravachol, Selektine, others
AHFS/Drugs.com Monograph
MedlinePlus a692025
License data
Pregnancy
category
  • AU:D
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 18% [2]
Protein binding 50% [2]
Metabolism Liver (minimal) [2]
Elimination half-life 1-3 hours [2]
Identifiers
  • (3R,5R)-3,5-dihydroxy-7-((1R,2S,6S,8R,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)-heptanoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.216.225 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C23H36O7
Molar mass 424.534 g·mol−1
3D model (JSmol)
  • O=C(O)C[C@H](O)C[C@H](O)CC[C@H]2[C@H](/C=C\C1=C\[C@@H](O)C[C@H](OC(=O)[C@@H](C)CC)[C@@H]12)C
  • InChI=1S/C23H36O7/c1-4-13(2)23(29)30-20-11-17(25)9-15-6-5-14(3)19(22(15)20)8-7-16(24)10-18(26)12-21(27)28/h5-6,9,13-14,16-20,22,24-26H,4,7-8,10-12H2,1-3H3,(H,27,28)/t13-,14-,16+,17+,18+,19-,20-,22-/m0/s1 Yes check.svgY
  • Key:TUZYXOIXSAXUGO-PZAWKZKUSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Pravastatin, sold under the brand name Pravachol among others, is a statin medication, used for preventing cardiovascular disease in those at high risk and treating abnormal lipids. [3] It is suggested to be used together with diet changes, exercise, and weight loss. [3] It is taken by mouth. [3]

Contents

Common side effects include joint pain, diarrhea, nausea, headaches, and muscle pains. [3] Serious side effects may include rhabdomyolysis, liver problems, and diabetes. [3] Use during pregnancy may harm the fetus. [3] Like all statins, pravastatin works by inhibiting HMG-CoA reductase, an enzyme found in liver that plays a role in producing cholesterol. [3]

Pravastatin was patented in 1980 and approved for medical use in 1989. [4] It is on the World Health Organization's List of Essential Medicines. [5] It is available as a generic medication. [3] In 2021, it was the 39th most commonly prescribed medication in the United States, with more than 15 million prescriptions. [6] [7]

Medical uses

Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease. [8] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels. [8]

Pravastatin has been shown to have a similar effectiveness at lowering low-density lipoprotein cholesterol as other statin medications such as fluvastatin but may low level evidence indicates that pravastatin may not be as effective as some other statin medications that are available. [9] The beneficial effect of pravastatin is dependent on the dose and the potential for side effects or unwanted effects from this medication are not clear from clinical trials. [9]

Adverse effects and contraindications

Pravastatin has undergone over 112,000 patient-years of double-blind, randomized trials using the 40  mg, once-daily dose and placebos. These trials indicate pravastatin is well tolerated and displays few noncardiovascular abnormalities in patients. [10] However, side effects may occur. A doctor should be consulted if symptoms such as heartburn or headache are severe and do not go away.[ medical citation needed ]

These uncommon side effects should be promptly reported to the prescribing doctor or an emergency medical service: [8]

These symptoms should be reported to the prescribing doctor if they persist or increase in severity:[ medical citation needed ]

Contraindications, conditions that warrant withholding treatment with pravastatin, include pregnancy and breastfeeding. [11] Taking pravastatin while pregnant could lead to birth defects. While the amount of pravastatin ingested by an infant from breastfeeding is low, patients breastfeeding should not take pravastatin due to potential effects on the infant's lipid metabolism. [12]

Drug interactions

Medications that should not be taken with pravastatin include, but are not limited to: [8] [11]

Pravastatin is cleared by the kidneys, giving it a distinct advantage over other statins when a potential for drug interactions using the hepatic pathway exists.[ medical citation needed ]

The combination of fenofibrate with pravastatin is approved for use in the European Union. [13]

Mechanism of action

Pravastatin acts as a lipoprotein-lowering drug through two pathways. In the major pathway, pravastatin inhibits the function of hydroxymethylglutaryl-CoA (HMG-CoA) reductase. As a reversible competitive inhibitor, pravastatin sterically hinders the action of HMG-CoA reductase by occupying the active site of the enzyme. Taking place primarily in the liver, this enzyme is responsible for the conversion of HMG-CoA to mevalonate in the rate-limiting step of the biosynthetic pathway for cholesterol. Pravastatin also inhibits the synthesis of very-low-density lipoproteins, which are the precursor to low-density lipoproteins (LDL). These reductions increase the number of cellular LDL receptors, thus LDL uptake increases, removing it from the bloodstream. [14] Overall, the result is a reduction in circulating cholesterol and LDL. A minor reduction in triglycerides and an increase in high-density lipoproteins (HDL) are common.

Pharmacokinetics

Oral bioavailability of pravastatin ranges from 17-34% with peak plasma concentration achieved 1-1.5 hours after administration. Absorption of drug is modestly decreased when taken with food however this does not reduce the clinical lipid-lowering effect. [15]

The 3α-hydroxyisomeric metabolite of pravastatin is also an active HMG-CoA reductase inhibitor with approximately 2.5-10% the potency of the parent compound. Pravastatin has a plasma half-life of 1.8 hours whereas this active metabolite has a half-life up to 77 hours. [15]

History

Initially known as CS-514, pravastatin is a derivative of ML236B (compactin), which was identified in a fungus called Penicillium citrinum in the 1970s by researchers of the Sankyo Pharma Inc. [16] It is being marketed outside Japan by the pharmaceutical company Bristol-Myers Squibb. In 2005, Pravachol was the 22nd-highest selling brand-name drug in the United States, with sales totaling $1.3 billion. [17]

The Food and Drug Administration (FDA) approved generic pravastatin for use in the United States on 24 April 2006. [17] Generic pravastatin sodium tablets were manufactured by Biocon Ltd, India and TEVA Pharmaceuticals in Kfar Sava, Israel. [17]

Related Research Articles

<span class="mw-page-title-main">Low-density lipoprotein</span> One of the five major groups of lipoprotein

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, very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). LDL delivers fat molecules to cells. LDL is involved in atherosclerosis, a process in which it is oxidized within the walls of arteries.

<span class="mw-page-title-main">Statin</span> Class of drugs used to lower cholesterol levels

Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most commonly prescribed cholesterol-lowering drugs.

<span class="mw-page-title-main">Fibrate</span> Class of chemical compounds

In pharmacology, the fibrates are a class of amphipathic carboxylic acids and esters. They are derivatives of fibric acid. They are used for a range of metabolic disorders, mainly hypercholesterolemia, and are therefore hypolipidemic agents.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

<span class="mw-page-title-main">Atorvastatin</span> Cholesterol-lowering medication

Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a first-line treatment. It is taken by mouth.

<span class="mw-page-title-main">Simvastatin</span> Lipid-lowering medication

Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart problems in those at high risk. It is taken by mouth.

<span class="mw-page-title-main">Fluvastatin</span> Chemical compound

Fluvastatin is a member of the statin drug class, used to treat hypercholesterolemia and to prevent cardiovascular disease.

<span class="mw-page-title-main">Rosuvastatin</span> Statin medication

Rosuvastatin, sold under the brand name Crestor among others, is a statin medication, used to prevent cardiovascular disease in those at high risk and treat abnormal lipids. It is recommended to be used together with dietary changes, exercise, and weight loss. It is taken orally.

<span class="mw-page-title-main">Lovastatin</span> Chemical compound

Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth.

<span class="mw-page-title-main">Cerivastatin</span> Chemical compound

Cerivastatin is a synthetic member of the class of statins used to lower cholesterol and prevent cardiovascular disease. It was marketed by the pharmaceutical company Bayer A.G. in the late 1990s, competing with Pfizer's highly successful atorvastatin (Lipitor). Cerivastatin was voluntarily withdrawn from the market worldwide in 2001, due to reports of fatal rhabdomyolysis.

<span class="mw-page-title-main">Gemfibrozil</span> Medication

Gemfibrozil, sold under the brand name Lopid among others, is a medication used to treat abnormal blood lipid levels. It is generally less preferred than statins. Use is recommended together with dietary changes and exercise. It is unclear if it changes the risk of heart disease. It is taken by mouth.

<span class="mw-page-title-main">Ezetimibe</span> Medication used to treat high cholesterol

Ezetimibe is a medication used to treat high blood cholesterol and certain other lipid abnormalities. Generally it is used together with dietary changes and a statin. Alone, it is less preferred than a statin. It is taken by mouth. It is also available in the fixed combinations ezetimibe/simvastatin, ezetimibe/atorvastatin, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid.

<span class="mw-page-title-main">HMG-CoA reductase</span> Mammalian protein found in Homo sapiens

HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids. HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia.

Hyperlipidemia is abnormally high levels of any or all lipids or lipoproteins in the blood. The term hyperlipidemia refers to the laboratory finding itself and is also used as an umbrella term covering any of various acquired or genetic disorders that result in that finding. Hyperlipidemia represents a subset of dyslipidemia and a superset of hypercholesterolemia. Hyperlipidemia is usually chronic and requires ongoing medication to control blood lipid levels.

<span class="mw-page-title-main">Fenofibrate</span> Drug of the fibrate class, mainly used to reduce cholesterol levels

Fenofibrate, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared than statins because it treats a different type of cholesterol abnormality to statins. While statins have strong evidence for reducing heart disease and death, there is evidence to suggest that fenofibrate also reduces the risk of heart disease and death. However, this seems only to apply to specific populations of people with elevated triglyceride levels and reduced high-density lipoprotein (HDL) cholesterol. Its use is recommended together with dietary changes.

<span class="mw-page-title-main">Mevastatin</span> Chemical compound

Mevastatin is a hypolipidemic agent that belongs to the statins class.

<span class="mw-page-title-main">Pitavastatin</span> Chemical compound

Pitavastatin is a member of the blood cholesterol lowering medication class of statins.

<span class="mw-page-title-main">Familial hypercholesterolemia</span> Genetic disorder characterized by high cholesterol levels

Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol, in the blood and early cardiovascular diseases. The most common mutations diminish the number of functional LDL receptors in the liver or produce abnormal LDL receptors that never go to the cell surface to function properly. Since the underlying body biochemistry is slightly different in individuals with FH, their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH. Nevertheless, treatment is usually effective.

The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular, cerebrovascular and peripheral vascular diseases. The statins inhibit cholesterol synthesis in the body and that leads to reduction in blood cholesterol levels, which is thought to reduce the risk of atherosclerosis and diseases caused by it.

Bempedoic acid, sold under the brand name Nexletol among others, is a medication for the treatment of hypercholesterolemia.

References

  1. ↑ Human Medicines Evaluation Division (26 November 2020). "Active substance: pravastatin" (PDF). List of nationally authorised medicinal products. European Medicines Agency.
  2. 1 2 3 4 Neuvonen PJ, Backman JT, Niemi M (2008). "Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin". Clinical Pharmacokinetics. 47 (7): 463–474. doi:10.2165/00003088-200847070-00003. PMID   18563955. S2CID   11716425.
  3. 1 2 3 4 5 6 7 8 "Pravastatin Sodium Monograph for Professionals". Drugs.com. AHFS. Retrieved 23 December 2018.
  4. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 472. ISBN   9783527607495.
  5. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  6. ↑ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  7. ↑ "Pravastatin - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  8. 1 2 3 4 "Pravachol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
  9. 1 2 Adams SP, Alaeiilkhchi N, Tasnim S, Wright JM, et al. (Cochrane Hypertension Group) (September 2023). "Pravastatin for lowering lipids". The Cochrane Database of Systematic Reviews. 2023 (9): CD013673. doi:10.1002/14651858.CD013673.pub2. PMC  10506175. PMID   37721222.
  10. ↑ Pfeffer MA, Keech A, Sacks FM, Cobbe SM, Tonkin A, Byington RP, et al. (May 2002). "Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project". Circulation. 105 (20): 2341–2346. doi: 10.1161/01.cir.0000017634.00171.24 . PMID   12021218.
  11. 1 2 Williams E. "Pravachol Side Effects Center". RxList. Retrieved 1 December 2012.
  12. ↑ "Pravastatin". LactMed. U.S. National Library of Medicine. Retrieved 1 December 2012.
  13. ↑ "Pravafenix EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 25 April 2020.
  14. ↑ Vaughan CJ, Gotto AM (August 2004). "Update on statins: 2003". Circulation. 110 (7): 886–892. doi: 10.1161/01.CIR.0000139312.10076.BA . PMID   15313959.
  15. 1 2 "DailyMed - PRAVASTATIN SODIUM tablet". dailymed.nlm.nih.gov. Retrieved 14 January 2024.
  16. ↑ Tobert JA (July 2003). "Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors". Nature Reviews. Drug Discovery. 2 (7): 517–526. doi:10.1038/nrd1112. PMID   12815379. S2CID   3344720.
  17. 1 2 3 "FDA Approves First Generic Pravastatin". Food and Drug Administration (FDA) (Press release). Archived from the original on 6 March 2010. Retrieved 20 January 2008.
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