Pravastatin

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Pravastatin
Pravastatin.svg
Systematic (IUPAC) name
(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
Clinical data
Trade namesPravachol
AHFS/Drugs.commonograph
MedlinePlusa692025
Pregnancy cat.D (AU) X (US)
Legal statusPrescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routesoral
Pharmacokinetic data
Bioavailability18%[1]
Protein binding50%[1]
MetabolismHepatic (minimal; CYP3A4-mediated)[1]
Half-life1-3 hours[1]
Identifiers
CAS number81093-37-0 YesY
ATC codeC10AA03
PubChemCID 54687
DrugBankDB00175
ChemSpider49398 YesY
UNIIKXO2KT9N0G YesY
ChEMBLCHEMBL1144 YesY
Chemical data
FormulaC23H36O7 
Mol. mass424.528 g/mol
 YesY (what is this?)  (verify)
 
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Pravastatin
Pravastatin.svg
Systematic (IUPAC) name
(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
Clinical data
Trade namesPravachol
AHFS/Drugs.commonograph
MedlinePlusa692025
Pregnancy cat.D (AU) X (US)
Legal statusPrescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Routesoral
Pharmacokinetic data
Bioavailability18%[1]
Protein binding50%[1]
MetabolismHepatic (minimal; CYP3A4-mediated)[1]
Half-life1-3 hours[1]
Identifiers
CAS number81093-37-0 YesY
ATC codeC10AA03
PubChemCID 54687
DrugBankDB00175
ChemSpider49398 YesY
UNIIKXO2KT9N0G YesY
ChEMBLCHEMBL1144 YesY
Chemical data
FormulaC23H36O7 
Mol. mass424.528 g/mol
 YesY (what is this?)  (verify)

Pravastatin (marketed as Pravachol or Selektine) is a member of the drug class of statins, used in combination with diet, exercise, and weight loss for lowering cholesterol and preventing cardiovascular disease.

Medical uses[edit]

Pravastatin is primarily used for the treatment of dyslipidemia and the prevention of cardiovascular disease.[2] It is recommended to be used only after other measures, such as diet, exercise, and weight reduction, have not improved cholesterol levels.[2]

The evidence for the use of pravastatin is generally weaker than for other statins. The antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT), failed to demonstrate a difference in all-cause mortality or nonfatal myocardial infarction/fatal coronary heart disease rates between patients receiving pravastatin 40 mg daily (a common starting dose) and those receiving usual care.[3]

Adverse effects and contraindications[edit]

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.[4] However, side effects may occur. A doctor should be consulted if symptoms such as heartburn or headache are severe and do not go away.

These uncommon side effects should be promptly reported to the prescribing doctor or an emergency medical service:[2]

These symptoms should be reported to the prescribing doctor if they persist or increase in severity:

Contraindications, conditions that warrant withholding treatment with pravastatin, include pregnancy and breastfeeding.[5] 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.[6]

Drug interactions[edit]

Medications that should not be taken with pravastatin include, but are not limited to:[2][5]

Pravastatin is cleared by the kidney, giving it a distinct advantage over other statins when a potential for drug interactions using the hepatic pathway exists.

Mechanism of action[edit]

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.[7] 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.

History[edit]

Initially known as CS-514, pravastatin is a derivative of ML236B (compactin), which was originally identified in a fungus called Penicillium citrinum in the 1970s by researchers of the Sankyo Pharma Inc.[8] It is presently 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.[9]

The U.S. Food and Drug Administration approved generic pravastatin for sale in the United States for the first time on April 24, 2006. Generic pravastatin sodium tablets are manufactured by Biocon Ltd, India and TEVA Pharmaceuticals in Kfar Sava, Israel.[9]

References[edit]

  1. ^ a b c d 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): 463–74. doi:10.2165/00003088-200847070-00003. PMID 18563955. 
  2. ^ a b c d "Prevachol". The American Society of Health-System Pharmacists. Retrieved 3 April 2011. 
  3. ^ No Authors Listed (2002). "Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT)". JAMA 288 (23): 2998–3007. doi:10.1001/jama.288.23.2998. PMID 12479764. 
  4. ^ Pfeffer MA, Keech A, Sacks FM, et al. “Safety and tolerability of pravastatin in long-term clinical trials: prospective Pravastatin Pooling (PPP) Project.” Circulation 2002;105:2341-2346
  5. ^ a b Williams, Eni. "Pravachol Side Effects Center". RxList. Retrieved 1 December 2012. 
  6. ^ "Pravastatin". LactMed. U.S. National Library of Medicine. Retrieved 1 December 2012. 
  7. ^ Vaughan, C. J., and A. M. Gotto, Jr. 2004. Update on statins: 2003. Circulation 110: 886–892.
  8. ^ Jonathan A. Tobert Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors Nature Reviews Drug Discovery 2, 517-526 (July 2003) PMID 12815379
  9. ^ a b "FDA Approves First Generic Pravastatin". Retrieved 2008-01-20. 

External links[edit]