Gemfibrozil - Wikipedia

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 ... Gemfibrozil FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch Medication GemfibrozilClinicaldataTradenamesLopid,Jezil,othersAHFS/Drugs.comMonographMedlinePlusa686002Licensedata US DailyMed: Gemfibrozil Pregnancycategory AU:B3 RoutesofadministrationBymouthATCcodeC10AB04(WHO)LegalstatusLegalstatus US:℞-only In general:℞ (Prescriptiononly) PharmacokineticdataBioavailabilityCloseto100%Proteinbinding95%MetabolismLiver(CYP3A4)Eliminationhalf-life1.5hoursExcretionKidney94%Feces6%Identifiers IUPACname 5-(2,5-dimethylphenoxy)-2,2-dimethyl-pentanoicacid CASNumber25812-30-0 YPubChemCID3463IUPHAR/BPS3439DrugBankDB01241 YChemSpider3345 YUNIIQ8X02027X3KEGGD00334 YChEBICHEBI:5296 YChEMBLChEMBL457 YCompToxDashboard(EPA)DTXSID0020652ECHAInfoCard100.042.968ChemicalandphysicaldataFormulaC15H22O3Molarmass250.338 g·mol−13Dmodel(JSmol)InteractiveimageMeltingpoint61to63 °C(142to145 °F) SMILES O=C(O)C(C)(C)CCCOc1cc(ccc1C)C InChI InChI=1S/C15H22O3/c1-11-6-7-12(2)13(10-11)18-9-5-8-15(3,4)14(16)17/h6-7,10H,5,8-9H2,1-4H3,(H,16,17) YKey:HEMJJKBWTPKOJG-UHFFFAOYSA-N Y   (verify) Gemfibrozil,soldunderthebrandnameLopidamongothers,isamedicationusedtotreatabnormalbloodlipidlevels.[1]Itisgenerallylesspreferredthanstatins.[1][2]Useisrecommendedtogetherwithdietarychangesandexercise.[1]Itisunclearifitchangestheriskofheartdisease.[1]Itistakenbymouth.[1] Commonsideeffectsincludeheadache,dizziness,feelingtired,andintestinalupset.[1]Serioussideeffectsmayincludeangioedema,gallstones,liverproblems,andmusclebreakdown.[1]Useinpregnancyandbreastfeedingisofunclearsafety.[3]Itbelongstothefibratesgroupofmedicationsandworksbydecreasingthebreakdownoflipidsinfatcells.[1] Gemfibrozilwaspatentedin1968andcameintomedicalusein1982.[4]Itisavailableasagenericmedication.[2]In2019,itwasthe212thmostcommonlyprescribedmedicationintheUnitedStates,withmorethan2 millionprescriptions.[5][6] Contents 1Medicaluses 2Sideeffects 3Contraindications 4Druginteractions 5Mechanismofactions 6History 7Environmentaldata 8References 9Furtherreading 10Externallinks Medicaluses[edit] Hyperlipidemia(TypeIII) Hypertriglyceridemia(TypeIV):Gemfibrozil,thoughnotaseffectiveasniacin(nicotinicacid,aformofVitaminB3),isbettertolerated.[citationneeded] Reducetriglyceridelevels[7] Reduceverylowdensitylipoprotein(VLDL)levels Modestreductionoflowdensitylipoprotein(LDL)levels Moderateincreaseinhighdensitylipoprotein(HDL)levels Sideeffects[edit] GIdistress Musculoskeletalpain Increasedincidenceofgallstone Hypokalemia(lowbloodpotassium) Increasedriskofcancer Contraindications[edit] Gemfibrozilshouldnotbegiventothesepatients:[citationneeded] Hepaticdysfunction Gemfibrozilshouldbeusedwithcautioninthesehigherriskcategories:[citationneeded] Biliarytractdisease Renaldysfunction Pregnantwomen Obesepatients Druginteractions[edit] Anticoagulants:Gemfibrozilpotentiatestheactionofwarfarinandindanedioneanticoagulants.[citationneeded] Statindrugs:Concomitantadministrationoffibrates(includinggemfibrozil)withstatindrugsincreasestheriskofmusclecramping,myopathy,andrhabdomyolysis.[8] Gemfibrozilinhibitstheactivationoftheliver'sCytochromeP450systemandCYP2C8,reducinghepaticmetabolismofmanydrugs,andprolongingtheirhalflivesanddurationofaction. DrugsmetabolizedbytheCytochromeP450systeminclude: Manyantidepressants Manyantipsychotics Manyantiepileptics Theophyllineandothermethylxanthinedrugs Severalanestheticagents Oralcontraceptivepills Statins Warfarin Selexipag Mechanismofactions[edit] Theexactmechanismofactionofgemfibrozilisunknown;however,severaltheoriesexistregardingtheverylowdensitylipoprotein(VLDL)effect;itcaninhibitlipolysisanddecreasesubsequenthepaticfattyaciduptakeaswellasinhibithepaticsecretionofVLDL;togethertheseactionsdecreaseserumVLDLlevelsandincreaseHDL-cholesterol;themechanismbehindHDLelevationiscurrentlyunknown. Gemfibrozilincreasestheactivityofextrahepaticlipoproteinlipase(LL),therebyincreasinglipoproteintriglyceridelipolysis.Itdoessobyactivatingperoxisomeproliferator-activatedreceptoralpha(PPARα)'transcriptionfactorligand',areceptorthatisinvolvedinmetabolismofcarbohydratesandfats,aswellasadiposetissuedifferentiation.Thisincreaseinthesynthesisoflipoproteinlipasetherebyincreasestheclearanceoftriglycerides.Chylomicronsaredegraded,VLDLsareconvertedtoLDLs,andLDLsareconvertedtoHDL.Thisisaccompaniedbyaslightincreaseinsecretionoflipidsintothebileandultimatelytheintestine.GemfibrozilalsoinhibitsthesynthesisandincreasestheclearanceofapolipoproteinB,acarriermoleculeforVLDL.[9] History[edit] GemfibrozilwasselectedfromaseriesofrelatedcompoundssynthesizedinthelaboratoriesoftheAmericancompanyParke-Davisinthelate1970s.Itcamefromresearchforcompoundsthatlowerplasmalipidlevelsinhumansandinanimals.[10] Environmentaldata[edit] Gemfibrozilhasbeendetectedinbiosolids(thesolidsremainingaftersewagetreatment)atconcentrationsupto2650 ng/gwetweight.[11]Thisindicatesthatitsurvivesthewastewatertreatmentprocess.Itisalsodetectedasenvironmentalpersistentmicropollutantinaquifersandingroundwatersinkarsticareas.[12] References[edit] ^abcdefgh"GemfibrozilMonographforProfessionals".Drugs.com.AmericanSocietyofHealth-SystemPharmacists.Retrieved3March2019. ^abBritishnationalformulary :BNF76(76 ed.).PharmaceuticalPress.2018.pp. 198–199.ISBN 9780857113382. ^"GemfibrozilUseDuringPregnancy".Drugs.com.Retrieved3March2019. ^FischerJ,GanellinCR(2006).Analogue-basedDrugDiscovery.JohnWiley&Sons.p. 474.ISBN 9783527607495. ^"TheTop300of2019".ClinCalc.Retrieved16October2021. ^"Gemfibrozil-DrugUsageStatistics".ClinCalc.Retrieved16October2021. ^"Gemfibrozil."WebMD.comAccessed14June2014.http://www.webmd.com/drugs/drug-11423-gemfibrozil+oral.aspx ^"MedicinesComplete".MedicinesComplete.BritishNationalFormulary.Retrieved1February2020. ^"Gemfibrozil". ^RodneyG,UhlendorfP,MaxwellRE(1976)."Thehypolipidaemiceffectofgemfibrozil(CI-719)inlaboratoryanimals".ProceedingsoftheRoyalSocietyofMedicine.69Suppl2(2_suppl):6–10.doi:10.1177/00359157760690S203.PMC 1864017.PMID 828263. ^"Biosolids".23April2014. ^DoummarJ,AounM(August2018)."Assessmentoftheoriginandtransportoffourselectedemergingmicropollutantssucralose,Acesulfame-K,gemfibrozil,andiohexolinakarstspringduringamulti-eventspringresponse".JournalofContaminantHydrology.215:11–20.Bibcode:2018JCHyd.215...11D.doi:10.1016/j.jconhyd.2018.06.003.PMID 29983209.S2CID 51599602. Furtherreading[edit] BellostaS,PaolettiR,CorsiniA(June2004)."Safetyofstatins:focusonclinicalpharmacokineticsanddruginteractions".Circulation.109(23Suppl1):III50-7.doi:10.1161/01.cir.0000131519.15067.1f.PMID 15198967. QuintanillaRodriguez,B.S.;Correa,R.(2020)."Gemfibrozil".StatPearls.NationalCenterforBiotechnologyInformation(NCBI).PMID 31424850.BookshelfID:NBK545266. Externallinks[edit] "Gemfibrozil".DrugInformationPortal.U.S.NationalLibraryofMedicine. "LopidInternationalStudy"(PDF).EuropeanMedicinesAgency.Archivedfromtheoriginal(PDF)on11June2007. "IndianHealthServiceNationalPharmacyandTherapeuticsCommitteeReviewofStatins,Fibrates,andNiacin"(PDF).IndianHealthService.SanDiego:U.S.DepartmentofHealthandHumanServices.12–13February2009.Archivedfromtheoriginal(PDF)on22June2014. vteLipid-modifyingagents(C10)GItractCholesterolabsorptioninhibitors,NPC1L1 Ezetimibe SCH-48461 Bileacidsequestrants/resins(LDL) Colesevelam Colestilan Colestipol Colestyramine Colextran LiverStatins(HMG-CoAreductase,LDL) Atorvastatin Cerivastatin‡ Fluvastatin Lovastatin Mevastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin# Niacinandderivatives(HDLandLDL) Acipimox Aluminiumnicotinate Niacin Niceritrol Nicofuranose Nicotinylalcohol MTTPinhibitors(VLDL) Dirlotapide Lomitapide Mitratapide ATPcitratelyaseinhibitors(LDL) Bempedoicacid BloodvesselsFibrates(PPAR) Aluminiumclofibrate Bezafibrate Cholinefenofibrate Ciprofibrate Clinofibrate Clofibrate‡ Clofibride Etofibrate Fenofibrate Gemfibrozil Nafenopin Pemafibrate Ronifibrate Simfibrate CETPinhibitors(HDL) Anacetrapib† Dalcetrapib§ Evacetrapib§ Obicetrapib† Torcetrapib§ PCSK9inhibitors(LDL) Alirocumab Bococizumab Evolocumab Combinations Amlodipine/atorvastatin Bempedoicacid/ezetimibe Ezetimibe/atorvastatin Ezetimibe/rosuvastatin Ezetimibe/simvastatin Fenofibrate/pravastatin Fenofibrate/simvastatin Niacin/laropiprant Niacin/lovastatin Niacin/simvastatin Other Alipogenetiparvovec Azacosterol Azalanstat Benfluorex‡ Darapladib§ Dextrothyroxine‡ Inclisiran Lapaquistat§ Magnesiumpyridoxal5-phosphateglutamate Meglutol Mipomersen Omega-3-triglycerides Policosanol Probucol Tiadenol Triparanol‡ Volanesorsen #WHO-EM ‡Withdrawnfrommarket Clinicaltrials: †PhaseIII §NevertophaseIII vtePPARmodulatorsPPARα Agonists:15-HETE 15-HpETE Aleglitazar Aluminiumclofibrate Arachidonicacid Bezafibrate Clofibrate CP-775146 Daidzein DHEA(prasterone)(inrodents) Elafibranor Etomoxir Fenofibrate Genistein Gemfibrozil GW-7647 Lanifibranor LeukotrieneB4 LG-101506 LG-100754 Lobeglitazone Muraglitazar Oleylethanolamide Palmitoylethanolamide Pemafibrate Perfluorononanoicacid Perfluorooctanoicacid Pioglitazone Saroglitazar Sodelglitazar Tesaglitazar Tetradecylthioaceticacid Troglitazone WY-14643 Antagonists:GW-6471 MK-886 PPARδ Agonists:15-HETE 15-HpETE Arachidonicacid Bezafibrate Daidzein Elafibranor Fonadelpar Genistein GW-0742 GW-501516 L-165,041 Lanifibranor LG-101506 Seladelpar Sodelglitazar Tetradecylthioaceticacid Antagonists:FH-535 GSK-0660 GSK-3787 PPARγ Agonists:5-Oxo-ETE 5-Oxo-15-hydroxy-ETE 15-Deoxy-Δ12,14-prostaglandinJ2 15-HETE 15-HpETE Aleglitazar Arachidonicacid Balaglitazone Berberine Bezafibrate Cannabidiol Cevoglitazar Ciglitazone Daidzein Darglitazone Edaglitazone Efatutazone Englitazone Etalocib Farglitazar Genistein GW-1929 Ibuprofen Imiglitazar Indeglitazar Lanifibranor LG-100268 LG-100754 LG-101506 Lobeglitazone Muraglitazar(muroglitazar) nTZDpa Naveglitazar Netoglitazone Oxeglitazar Peliglitazar Pemaglitazar Perfluorononanoicacid Pioglitazone ProstaglandinJ2 Ragaglitazar Reglitazar Rivoglitazone Rosiglitazone RS5444 Saroglitazar Sipoglitazar Sodelglitazar Telmisartan Tesaglitazar Troglitazone SPPARMs:BADGE EPI-001 INT-131 MK-0533 S26948 Antagonists:FH-535 GW-9662 SR-202 T-0070907 Unknown:SR-1664 Non-selective Agonists:Ciprofibrate Clinofibrate Clofibride Englitazone Etofibrate Farglitazar Netoglitazone Ronifibrate Rivoglitazone Simfibrate Seealso Receptor/signalingmodulators Portal: Medicine Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Gemfibrozil&oldid=1096515965" Categories:FibratesPhenolethersCarboxylicacidsCYP2C8inhibitorsHiddencategories:CS1:longvolumevalueArticleswithshortdescriptionShortdescriptionisdifferentfromWikidataUsedmydatesfromAugust2021Drugswithnon-standardlegalstatusECHAInfoCardIDfromWikidataDrugboxeswhichcontainchangestowatchedfieldsAllarticleswithunsourcedstatementsArticleswithunsourcedstatementsfromDecember2012Wikipediamedicinearticlesreadytotranslate Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Inotherprojects WikimediaCommons Languages العربيةتۆرکجهCymraegDeutschEspañolفارسیFrançaisHrvatskiItalianoMagyarNederlands日本語ଓଡ଼ିଆPolskiPortuguêsRomânăРусскийСрпски/srpskiSrpskohrvatski/српскохрватскиSuomiSvenskaไทยTiếngViệt Editlinks