Gemfibrozil

Gemfibrozil, sold under the brand name Lopid among others, is a medication used to treat abnormal blood lipid levels.[1] Its is generally less preferred than statins.[1][2] Use is recommended together with dietary changes and exercise.[1] It is unclear if it changes the risk of heart disease.[1] It is taken by mouth.[1]

Gemfibrozil
Clinical data
Trade namesLopid, Jezil, others
AHFS/Drugs.comMonograph
MedlinePlusa686002
Pregnancy
category
  • US: C (Risk not ruled out)
    Routes of
    administration    		By mouth
    ATC code
    Legal status
    Legal status
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    BioavailabilityClose to 100%
    Protein binding95%
    MetabolismHepatic (CYP3A4)
    Elimination half-life1.5 hours
    ExcretionRenal 94%
    Feces 6%
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEBI
    ChEMBL
    CompTox Dashboard (EPA)
    ECHA InfoCard100.042.968
    Chemical and physical data
    FormulaC15H22O3
    Molar mass250.333 g/mol g·mol−1
    3D model (JSmol)
    Melting point61 to 63 °C (142 to 145 °F)
      (verify)

    Common side effects include headache, dizziness, feeling tired, and intestinal upset.[1] Serious side effects may include angioedema, gallstones, liver problems, and muscle breakdown.[1] Use in pregnancy and breastfeeding is of unclear safety.[3] It belongs to the fibrates group of medications and works by decreasing the breakdown of lipids in fat cells.[1]

    Gemfibrozil was patented in 1968 and came into medical medical use in 1982.[4] It is available as a generic medication.[2] A month supply in the United Kingdom costs the NHS about 30 £ as of 2019.[2] In the United States the wholesale cost of this amount is about 6 USD.[5] In 2016 it was the 132nd most prescribed medication in the United States with more than 5 million prescriptions.[6]

    Medical uses

    Side effects

    Contraindications
    • Gemfibrozil should not be given to these patients:
      • Hepatic dysfunction
    • Gemfibrozil should be used with caution in these higher risk categories:
      • Biliary tract disease
      • Renal dysfunction
      • Pregnant women
      • Obese patients

    Drug interactions
    • Anticoagulants: Gemfibrozil potentiates the action of warfarin and indanedione anticoagulants.
    • Statin drugs: Concomitant administration of fibrates (including gemfibrozil) with statin drugs increases the risk of muscle cramping, myopathy, and rhabdomyolysis.
    • Gemfibrozil inhibits the activation of the liver's Cytochrome P450 system and CYP2C8, reducing hepatic metabolism of many drugs, and prolonging their half lives and duration of action.

    Mechanism of actions

    The exact mechanism of action of gemfibrozil is unknown; however, several theories exist regarding the very low density lipoprotein (VLDL) effect; it can inhibit lipolysis and decrease subsequent hepatic fatty acid uptake as well as inhibit hepatic secretion of VLDL; together these actions decrease serum VLDL levels and increase HDL-cholesterol; the mechanism behind HDL elevation is currently unknown.

    Gemfibrozil increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. It does so by activating peroxisome proliferator-activated receptor alpha (PPARα) 'transcription factor ligand', a receptor that is involved in metabolism of carbohydrates and fats, as well as adipose tissue differentiation. This increase in the synthesis of lipoprotein lipase thereby increases the clearance of triglycerides. Chylomicrons are degraded, VLDLs are converted to LDLs, and LDLs are converted to HDL. This is accompanied by a slight increase in secretion of lipids into the bile and ultimately the intestine. Gemfibrozil also inhibits the synthesis and increases the clearance of apolipoprotein B, a carrier molecule for VLDL.[8]

    History

    Gemfibrozil was selected from a series of related compounds synthesized in the laboratories of the American company Parke-Davis in the late 1970s. It came from research for compounds that lower plasma lipid levels in humans and in animals.[9]

    Environmental data

    Gemfibrozil has been detected in biosolids (the solids remaining after sewage treatment) at concentrations up to 2650 ng/g wet weight.[10] This indicates that it survives the wastewater treatment process. It is also detected as environmental persistent micropollutant in aquifers and in groundwaters in karstic areas.[11]

    References
    1. "Gemfibrozil Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.
    2. British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 198–199. ISBN 9780857113382.
    3. "Gemfibrozil Use During Pregnancy". Drugs.com. Retrieved 3 March 2019.
    4. Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 474. ISBN 9783527607495.
    5. "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Retrieved 3 March 2019.
    6. "The Top 300 of 2019". clincalc.com. Retrieved 22 December 2018.
    7. "Gemfibrozil." WebMD.com Accessed 14 June 2014. http://www.webmd.com/drugs/drug-11423-gemfibrozil+oral.aspx
    8. https://pubchem.ncbi.nlm.nih.gov/compound/gemfibrozil#section=Mechanism-of-Action
    9. Rodney, G; et al. (1976). "The Hypolipidemic Effect of Gemfibrozil (CI-719) in Laboratory Animals". Proc. R. Soc. Med. 69 (Supplement 2): 6–9. PMC 1864017. PMID 828263.
    10. http://water.epa.gov/scitech/wastetech/biosolids/tnsss-overview.cfm
    11. Doummar, Joanna; Aoun, Michel (2018-08-01). "Assessment of the origin and transport of four selected emerging micropollutants sucralose, Acesulfame-K, gemfibrozil, and iohexol in a karst spring during a multi-event spring response". Journal of Contaminant Hydrology. 215: 11–20. Bibcode:2018JCHyd.215...11D. doi:10.1016/j.jconhyd.2018.06.003. ISSN 0169-7722. PMID 29983209.
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