Fluvastatin

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Fluvastatin
Fluvastatin2DCSD.svg
Systematic (IUPAC) name
(3R,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
Clinical data
Trade names Lescol
AHFS/Drugs.com Monograph
MedlinePlus a694010
Pregnancy
category
  • AU: D
  • US: X (Contraindicated)
Routes of
administration
Oral
Legal status
Legal status
Pharmacokinetic data
Bioavailability 24–30%[1][2]
Protein binding >98%[2]
Metabolism Hepatic (CYP2C9 (75%), CYP2C8 (5%), CYP3A4 (20%))[2][3]
Biological half-life 1–3 hours (capsule), 9 hours (XR)[2][3]
Excretion Faeces (95%), urine (5%)[2]
Identifiers
CAS Number 93957-54-1 YesY
ATC code C10AA04 (WHO)
PubChem CID 446155
IUPHAR/BPS 2951
DrugBank DB01095 YesY
ChemSpider 393587 YesY
UNII 4L066368AS YesY
KEGG D07983 YesY
ChEBI CHEBI:38565 YesY
ChEMBL CHEMBL1078 YesY
Chemical data
Formula C24H26FNO4
Molar mass 411.466 g/mol
  (verify)

Fluvastatin (trade names Lescol, Canef, Vastin) is a member of the statin drug class, used to treat hypercholesterolemia and to prevent cardiovascular disease.

Adverse effects[edit]

Adverse effects are comparable to other statins. Common are nausea, indigestion, insomnia and headache. Myalgia (muscle pain), and rarely rhabdomyolysis, characteristic side effects for statins, can also occur.[4]

Interactions[edit]

Contrary to lovastatin, simvastatin and atorvastatin, fluvastatin has no relevant interactions with drugs that inhibit the liver enzyme CYP3A4, and a generally lower potential for interactions than most other statins. Fluconazole, a potent inhibitor of CYP2C9, does increase fluvastatin levels.[4]

Pharmacology[edit]

Mechanism of action[edit]

Main article: Statin

Fluvastatin works by blocking the liver enzyme HMG-CoA reductase, which facilitates an important step in cholesterol synthesis.[1]

Pharmacokinetics[edit]

The drug is quickly and almost completely (98%) absorbed from the gut. Food intake slows down absorption, but does not decrease it. Due to its first-pass effect, bioavailability is lower: about 24[1]–30%[2] according to different sources. Over 98% of the substance is bound to plasma proteins.[1]

Several cytochrome P450 enzymes (mainly CYP2C9, but also CYP3A4 and CYP2C8[5]) are involved in the metabolism of fluvastatin, which makes is less liable to interactions than most other statins. The main metabolite is inactive and is called "N-desisopropyl propionic acid" in the literature.[1][4]

93–95% of the drug are excreted via the faeces, less than 2% of which in form of the original substance.[1]

Research[edit]

Fluvastatin has also been shown to exhibit antiviral activity against hepatitis C in a study with 31 patients. This effect has been described as modest, variable, and often short-lived, by the authors.[6]

References[edit]

  1. ^ a b c d e f Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 
  2. ^ a b c d e f 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. 
  3. ^ a b "Lescol, Lescol XR (fluvastatin) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. Retrieved 18 March 2014. 
  4. ^ a b c Dinnendahl, V, Fricke, U, eds. (2012). "Arzneistoff-Profile" (in German). 2 (26 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3. 
  5. ^ Lescol Monograph on Drugs.com.
  6. ^ Bader T, Fazili J, Madhoun M, et al. (April 2008). "Fluvastatin Inhibits Hepatitis C Replication in Humans". Am. J. Gastroenterol. 103 (6): 1383–9. doi:10.1111/j.1572-0241.2008.01876.x. PMID 18410471.