Identification

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Name
Gemfibrozil
Accession Number
DB01241  (APRD00293)
Type
Small Molecule
Groups
Approved
Description

Gemfibrozil is a fibric acid agent, similar to clofibrate, used to treat Type IIb, IV, and V hyperlipidemias.3,11 Gemfibrozil is not a first line treatment and is prescribed to patients who have not responded adequately to weight loss, diet, exercise, and other medications.11

Gemfibrozil was granted FDA approval on 21 December 1981.11

Structure
Thumb
Synonyms
  • 2,2-Dimethyl-5-(2,5-dimethylphenoxy)valeriansäure
  • 2,2-Dimethyl-5-(2,5-xylyloxy)valeriansäure
  • 2,2-Dimethyl-5-(2,5-xylyloxy)valeric acid
  • Gemfibrozil
  • Gemfibrozilo
  • Gemfibrozilum
External IDs
CI-719
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GemfibrozilTablet600 mg/1OralWatson Pharmaceuticals2007-01-01Not applicableUs
Gemfibrozil Cap 300mgCapsuleOralOmni Laboratories Division, Warner Lambert Canada Inc.1990-12-312003-07-04Canada
Gemfibrozil Tab 600mgTabletOralOmni Laboratories Division, Warner Lambert Canada Inc.1991-12-312003-07-04Canada
Gemfibrozil-300 - CapCapsuleOralPro Doc Limitee1995-12-312010-07-13Canada
Gemfibrozil-600 - Tab 600mgTabletOralPro Doc Limitee1995-12-312015-07-10Canada
LopidTablet, film coated600 mg/1OralREMEDYREPACK INC.2017-08-16Not applicableUs
LopidTablet, film coated600 mg/1OralParke Davis Div Of Pfizer Inc2004-03-30Not applicableUs
LopidTablet, film coated600 mg/1OralPhysicians Total Care, Inc.2004-03-302012-06-30Us
Lopid 600mgTabletOralPfizer Canada Ulc1987-12-312013-07-18Canada
Lopid Cap 300mgCapsuleOralPfizer Canada Ulc1984-12-312013-07-18Canada
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-gemfibrozilTabletOralApotex Corporation1993-12-31Not applicableCanada
Apo-gemfibrozil Cap 300mg USPCapsuleOralApotex Corporation1993-12-31Not applicableCanada
Dom-gemfibrozilTabletOralDominion Pharmacal1998-10-222013-04-05Canada
Dom-gemfibrozilCapsuleOralDominion Pharmacal2000-03-10Not applicableCanada
GemfibrozilTablet600 mg/1OralA S Medication Solutions2011-01-01Not applicableUs54569 369520180907 15195 d50gg9
GemfibrozilTablet600 mg/1OralCadila Pharnmaceuticals2016-06-172017-03-22Us
GemfibrozilTablet600 mg/1OralPreferreed Pharmaceuticals Inc.2011-01-01Not applicableUs68788 914920180913 8702 qyrptq
GemfibrozilTablet, film coated600 mg/1OralExelan Pharmaceuticals, Inc.2006-10-20Not applicableUs
GemfibrozilTablet, film coated600 mg/1Oralbryant ranch prepack1998-10-01Not applicableUs
GemfibrozilTablet600 mg/1OralCarilion Materials Management2011-01-01Not applicableUs68151 289320180907 15195 1twsrt8
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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International/Other Brands
Gemlipid (Farmellas Enterprises) / Gen-Fibro / Genlip (Teofarma) / Jezil / Lipur (Pfizer)
Categories
UNII
Q8X02027X3
CAS number
25812-30-0
Weight
Average: 250.3334
Monoisotopic: 250.15689457
Chemical Formula
C15H22O3
InChI Key
HEMJJKBWTPKOJG-UHFFFAOYSA-N
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)
IUPAC Name
5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
SMILES
CC1=CC(OCCCC(C)(C)C(O)=O)=C(C)C=C1

Pharmacology

Indication

Gemfibrozil is indicated to treat patients with Types IV and V hyperlipidemia who have elevated serum triglycerides (usually above 2000mg/dL), elevated VLDL cholesterol, fasting chylomicrons, are at risk of developing pancreatitis, and do not adequately respond to dietary restrictions.11 Gemfibrozil is also indicated to reduce the risk of developing coronary heart disease in patients with Type IIb hyperlipidemia without history or symptoms of coronary heart disease; who do not adequately respond to weight loss, diet, exercise, and other medications; and have low HDL, raised LDL, and raised triglycerides.11

Associated Conditions
Pharmacodynamics

Gemfibrozil alters lipid metabolism to treat patients with hyperlipidemia.11 The duration of action requires twice daily dosing as the mean residence time of gemfibrozil is up to 9.6h in patients with chronic renal failure.7 Gemfibrozil has a wide therapeutic index as trials with twice the standard dose were not associated with severe side effects.8,11 Patients taking gemfibrozil may be at an increased risk of developing cholelithiasis and cholecystitis, as seen in patients taking clofibrate.11

Mechanism of action

Gemfibrozil activates peroxisome proliferator-activated receptor-α (PPARα), which alters lipid metabolism.3 This activation leads to increased HDL, apo AI, apo AII, lipoprotein lipase (LPL), inhibition of apo B synthesis, peripheral lipolysis, decreased removal of free fatty acids by the liver, and increased clearance of apoB.1,3,11

Upregulated LPL reduces plasma triglyceride levels.1,3,11 Decreased hepatic removal of fatty acids decreases the production of triglycerides.1,3,11 The effects on apoB synthesis and clearance decrease VLDL production which also reduce plasma triglyceride levels.1,3,11

Gemfibrozil's glucuronide metabolite is also an inhibitor of CYP2C8.4

TargetActionsOrganism
APeroxisome proliferator-activated receptor alpha
agonist
Humans
USolute carrier organic anion transporter family member 1B1
inhibitor
Humans
USolute carrier family 22 member 8
inhibitor
Humans
USolute carrier organic anion transporter family member 2B1
inhibitor
Humans
USolute carrier organic anion transporter family member 1B3
inhibitor
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Gemfibrozil is absorbed from the gastrointestinal tract.11

In healthy volunteers, a 900mg oral dose of gemfibrozil has a Cmax of 46±16µg/mL with a Tmax of 2.2±1.1h.7 In patients with chronic renal failure, gemfibrozil has a Cmax of 13.8±11.1µg/mL with a Tmax of 2.3±1.0h.7 In patients with liver disease, gemfibrozil has a Cmax of 23.0±10.3µg/mL with a Tmax of 2.6±1.7h.7

Volume of distribution

The volume of distribution of gemfibrozil is estimated to be 0.8L/kg.10

Protein binding

Gemfibrozil is 99% protein bound.3,6 It is 98.6% bound to serum albumin, 0.8% bound to erythrocytes, and 0.8% unbound.5,6 There is negligible binding to alpha-1-acid glycoprotein.6

Metabolism

Gemfibrozil undergoes hydroxylation at the 5'-methyl and 4' positions to form the M1 and M2 metaolites respectively9. Gemfibrozil also undergoes O-glucuronidation to form gemfibrozil 1-beta glucuronide, an inhibitor of CYP2C8.4 This O-glucuronidation is primarily mediated by UGT2B7, but also by UGT1A1, UGT1A3, UGT1A9, UGT2B4, UGT2B17.4

Route of elimination

Approximately 70% of a dose of gemfibrozil is eliminated in the urine.11 The majority of a dose is eliminated as a glucuronide conjugate and <2% is elimiinated as the unmetabolized drug.11 6% of a dose is eliminated in the feces.11

In healthy volunteers, 0.02-0.15% of a dose was detected in the urine as unmetabolized gemfibrozil, with 7-14% detected as conjugated metabolites.7 In patients with renal failure, trace amounts of unmetabolized gemfibrozil is present in the urine, with 0.5-9.8% detected as conjugated metabolites.7 In patients with liver disease, 0.1-0.2% of a dose was detected in the urine as unmetabolized gemfibrozil, with 25-50% detected as conjugated metabolites.7

Half life

Gemfibrozil has a plasma half-life of 1.5 hours.11 In patients with renal failure the half life is 2.4h and in patients with liver disease the half life is 2.1h.7

Clearance

The clearance of gemfibrozil is estimated to be 6.0L/h.10

Toxicity

The oral TDLO of gemfibrozil in humans is 18gm/kg/3Y.12 The oral LD50 in mice is 2218mg/kg and in rats is 1414mg/kg.12 The intraperitoneal LD50 in rats is 445mg/kg.12

Patients experiencing an overdose may present with abdominal cramps, adnormal liver function tests, diarrhea, increased CPK, joint and muscle pain, nausea, and vomiting.11 Patients should be treated with symptomatic and supportive measures.11

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Gemfibrozil.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Gemfibrozil.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Gemfibrozil.
8-azaguanineThe metabolism of 8-azaguanine can be decreased when combined with Gemfibrozil.
8-chlorotheophyllineThe metabolism of 8-chlorotheophylline can be decreased when combined with Gemfibrozil.
9-DeazaguanineThe metabolism of 9-Deazaguanine can be decreased when combined with Gemfibrozil.
9-MethylguanineThe metabolism of 9-Methylguanine can be decreased when combined with Gemfibrozil.
AbacavirThe metabolism of Abacavir can be decreased when combined with Gemfibrozil.
AcarboseAcarbose may decrease the excretion rate of Gemfibrozil which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Gemfibrozil which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
  • Take 30 minutes before meals.

References

Synthesis Reference

Gianfranco Piccoli, Antonio Tarquini, Giovanni Frare, "Process for the preparation of gemfibrozil." U.S. Patent US5654476, issued May, 1980.

US5654476
General References
  1. Saku K, Gartside PS, Hynd BA, Kashyap ML: Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest. 1985 May;75(5):1702-12. doi: 10.1172/JCI111879. [PubMed:3923042]
  2. Okerholm RA, Keeley FJ, Peterson FE, Glazko AJ: The metabolism of gemfibrozil. Proc R Soc Med. 1976;69 Suppl 2:11-4. [PubMed:828261]
  3. Quintanilla Rodriguez BS, Correa R: Gemfibrozil . [PubMed:31424850]
  4. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]
  5. Sallustio BC, Fairchild BA, Pannall PR: Interaction of human serum albumin with the electrophilic metabolite 1-O-gemfibrozil-beta-D-glucuronide. Drug Metab Dispos. 1997 Jan;25(1):55-60. [PubMed:9010630]
  6. Hamberger C, Barre J, Zini R, Taiclet A, Houin G, Tillement JP: In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs. Int J Clin Pharmacol Res. 1986;6(6):441-9. [PubMed:3468088]
  7. Knauf H, Kolle EU, Mutschler E: Gemfibrozil absorption and elimination in kidney and liver disease. Klin Wochenschr. 1990 Jul 5;68(13):692-8. doi: 10.1007/bf01667018. [PubMed:2381138]
  8. Fereshetian AG, Davidson M, Haber H, Black DM: Gemfibrozil treatment in patients with elevated lipoprotein a: a pilot study. Clin Drug Investig. 1998;16(1):1-7. doi: 10.2165/00044011-199816010-00001. [PubMed:18370512]
  9. Takahiro M, Haruo I, Toshihiko, I: Identification of Gemfibrozil Metabolites, Produced as Positional Isomers in Human Liver Microsomes, by On-line Analyses Using Liquid Chromatography/Mass Spectrometry and Liquid Chromatography/Nuclear Magnetic Resonance Spectroscopy J. Mass Spectrom. Soc. Jpn.. 2004 Jun 6;52(5):277-283.
  10. Varma MV, Lin J, Bi YA, Kimoto E, Rodrigues AD: Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-beta-Glucuronide. Drug Metab Dispos. 2015 Jul;43(7):1108-18. doi: 10.1124/dmd.115.064303. Epub 2015 May 4. [PubMed:25941268]
  11. FDA Approved Drug Products: Gemfibrozil Oral Tablets [Link]
  12. Cayman Chemicals: Gemfibrozil MSDS [Link]
External Links
Human Metabolome Database
HMDB0015371
KEGG Drug
D00334
KEGG Compound
C07020
PubChem Compound
3463
PubChem Substance
46508264
ChemSpider
3345
BindingDB
50110590
ChEBI
5296
ChEMBL
CHEMBL457
Therapeutic Targets Database
DAP000210
PharmGKB
PA449750
Guide to Pharmacology
GtP Drug Page
HET
4TX
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Gemfibrozil
ATC Codes
C10AB04 — Gemfibrozil
AHFS Codes
  • 24:06.06 — Fribic Acid Derivatives
PDB Entries
5boj
FDA label
Download (260 KB)
MSDS
Download (74.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedPreventionPreclinical Alzheimer's Disease1
1CompletedNot AvailableDrug Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics1
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceDrug Drug Interaction (DDI) / Healthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedOtherAnemias1
1CompletedTreatmentBioavailability1
1CompletedTreatmentDrug Drug Interaction (DDI)1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentHypertriglyceridemias1
1CompletedTreatmentMalignancies1
1CompletedTreatmentType 2 Diabetes Mellitus2
1RecruitingTreatmentHealthy Adult Subjects1
2CompletedTreatmentCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / Myocardial Ischemia1
2CompletedTreatmentCessation, Smoking1
2CompletedTreatmentNicotine Dependence1
2TerminatedTreatmentAlcohol Use Disorder (AUD)1
3CompletedTreatmentCoronary Heart Disease (CHD)1
4CompletedTreatmentHealthy Volunteers1
4WithdrawnTreatmentAtherosclerosis1
Not AvailableCompletedNot AvailableHealthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Ancheng Pharma Limited
  • Apotex Inc.
  • Blu Pharmaceuticals LLC
  • Bryant Ranch Prepack
  • Camber Pharmaceuticals Inc.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • DAVA Pharmaceuticals
  • Dept Health Central Pharmacy
  • DHHS Program Support Center Supply Service Center
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Global Pharmaceuticals
  • Golden State Medical Supply Inc.
  • Heartland Repack Services LLC
  • InvaGen Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Liberty Pharmaceuticals
  • Major Pharmaceuticals
  • Murfreesboro Pharmaceutical Nursing Supply
  • Norwich Pharmaceuticals Inc.
  • Novopharm Ltd.
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Professional Co.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Southwood Pharmaceuticals
  • Sun Pharmaceutical Industries Ltd.
  • Teva Pharmaceutical Industries Ltd.
  • Torpharm Inc.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
  • Zydus Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral600 mg/1
Tablet, coatedOral600 mg/1
Tablet, film coatedOral600 mg/1
CapsuleOral
TabletOral
Prices
Unit descriptionCostUnit
Gemfibrozil powder2.88USD g
Lopid 600 mg tablet2.07USD tablet
Gemfibrozil 600 mg tablet1.8USD tablet
Apo-Gemfibrozil 600 mg Tablet0.65USD tablet
Mylan-Gemfibrozil 600 mg Tablet0.65USD tablet
Novo-Gemfibrozil 600 mg Tablet0.65USD tablet
Nu-Gemfibrozil 600 mg Tablet0.65USD tablet
Pms-Gemfibrozil 600 mg Tablet0.65USD tablet
Lopid 300 mg Capsule0.58USD capsule
Apo-Gemfibrozil 300 mg Capsule0.31USD capsule
Mylan-Gemfibrozil 300 mg Capsule0.31USD capsule
Novo-Gemfibrozil 300 mg Capsule0.31USD capsule
Nu-Gemfibrozil 300 mg Capsule0.31USD capsule
Pms-Gemfibrozil 300 mg Capsule0.31USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)58-61FDA Label
boiling point (°C)158.5 °C at 2.00E-02 mm HgPhysProp
logP4.387ChemSpider
Predicted Properties
PropertyValueSource
Water Solubility0.0278 mg/mLALOGPS
logP3.61ALOGPS
logP4.39ChemAxon
logS-4ALOGPS
pKa (Strongest Acidic)4.42ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity71.82 m3·mol-1ChemAxon
Polarizability28.9 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.977
Blood Brain Barrier+0.9213
Caco-2 permeable+0.7918
P-glycoprotein substrateSubstrate0.5597
P-glycoprotein inhibitor INon-inhibitor0.8943
P-glycoprotein inhibitor IINon-inhibitor0.8839
Renal organic cation transporterNon-inhibitor0.8177
CYP450 2C9 substrateNon-substrate0.7512
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6973
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8949
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8234
Ames testNon AMES toxic0.7822
CarcinogenicityNon-carcinogens0.8314
BiodegradationNot ready biodegradable0.6759
Rat acute toxicity2.2167 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9774
hERG inhibition (predictor II)Non-inhibitor0.8701
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-24b892a8bd68bdf9cef6
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-7a9eaaae65f0e1efcbc4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-12b36ea4be2a1b876c61
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-647692900acca2ec2441
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-41c8e4e08162dfaf1fc4
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-0900000000-28d25da91cc1d391cc84
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-00di-0900000000-a08267bdc97edb1a2601
LC-MS/MS Spectrum - LC-ESI-ITFT , negativeLC-MS/MSsplash10-00di-0900000000-a133a90a69b988c45ffb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0059-6910000000-0ad597adcb83e9f4e4ba
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0059-8900000000-8684ba342d3eb0a7f602
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05cr-9400000000-008385b887cc6ac6d748
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ac0-9300000000-74e1b5c007dd49af6a01
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0ab9-9200000000-cc36aaee7c70d8e92f96
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9100000000-ce28ed926945c33079d6
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
p-Xylenes / Phenoxy compounds / Alkyl aryl ethers / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Phenoxy compound / P-xylene / Xylene / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / Carboxylic acid derivative / Carboxylic acid / Ether / Monocarboxylic acid or derivatives
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether (CHEBI:5296)

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Clavey V, Copin C, Mariotte MC, Bauge E, Chinetti G, Fruchart J, Fruchart JC, Dallongeville J, Staels B: Cell culture conditions determine apolipoprotein CIII secretion and regulation by fibrates in human hepatoma HepG2 cells. Cell Physiol Biochem. 1999;9(3):139-49. [PubMed:10494028]
  2. Bosse Y, Pascot A, Dumont M, Brochu M, Prud'homme D, Bergeron J, Despres JP, Vohl MC: Influences of the PPAR alpha-L162V polymorphism on plasma HDL(2)-cholesterol response of abdominally obese men treated with gemfibrozil. Genet Med. 2002 Jul-Aug;4(4):311-5. [PubMed:12172398]
  3. Pahan K, Jana M, Liu X, Taylor BS, Wood C, Fischer SM: Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes. J Biol Chem. 2002 Nov 29;277(48):45984-91. Epub 2002 Sep 18. [PubMed:12244038]
  4. Shoji Y, Sanekata A, Sato M, Imaizumi K: Preparation of antiserum against rat delta6-desaturase and its use to evaluate the desaturase protein levels in rats treated with gemfibrozil, a ligand for peroxisome proliferator-activated receptor alpha. Biosci Biotechnol Biochem. 2003 May;67(5):1177-8. [PubMed:12834305]
  5. Rizvi F, Iftikhar M, George JP: Beneficial effects of fish liver preparations of sea bass (Lates calcarifer) versus gemfibrozil in high fat diet-induced lipid-intolerant rats. J Med Food. 2003 Summer;6(2):123-8. [PubMed:12935323]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Sharma P, Holmes VE, Elsby R, Lambert C, Surry D: Validation of cell-based OATP1B1 assays to assess drug transport and the potential for drug-drug interaction to support regulatory submissions. Xenobiotica. 2010 Jan;40(1):24-37. doi: 10.3109/00498250903351013. [PubMed:19919292]
  2. Varma MV, Lin J, Bi YA, Kimoto E, Rodrigues AD: Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-beta-Glucuronide. Drug Metab Dispos. 2015 Jul;43(7):1108-18. doi: 10.1124/dmd.115.064303. Epub 2015 May 4. [PubMed:25941268]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Varma MV, Lin J, Bi YA, Kimoto E, Rodrigues AD: Quantitative Rationalization of Gemfibrozil Drug Interactions: Consideration of Transporters-Enzyme Interplay and the Role of Circulating Metabolite Gemfibrozil 1-O-beta-Glucuronide. Drug Metab Dispos. 2015 Jul;43(7):1108-18. doi: 10.1124/dmd.115.064303. Epub 2015 May 4. [PubMed:25941268]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Noe J, Portmann R, Brun ME, Funk C: Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14. doi: 10.1124/dmd.106.012930. Epub 2007 Apr 30. [PubMed:17470528]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Noe J, Portmann R, Brun ME, Funk C: Substrate-dependent drug-drug interactions between gemfibrozil, fluvastatin and other organic anion-transporting peptide (OATP) substrates on OATP1B1, OATP2B1, and OATP1B3. Drug Metab Dispos. 2007 Aug;35(8):1308-14. doi: 10.1124/dmd.106.012930. Epub 2007 Apr 30. [PubMed:17470528]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Honkalammi J, Niemi M, Neuvonen PJ, Backman JT: Gemfibrozil is a strong inactivator of CYP2C8 in very small multiple doses. Clin Pharmacol Ther. 2012 May;91(5):846-55. doi: 10.1038/clpt.2011.313. [PubMed:22472994]
  2. Wang JS, Neuvonen M, Wen X, Backman JT, Neuvonen PJ: Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos. 2002 Dec;30(12):1352-6. [PubMed:12433802]
  3. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Wen X, Wang JS, Backman JT, Kivisto KT, Neuvonen PJ: Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos. 2001 Nov;29(11):1359-61. [PubMed:11602509]
Details
3. Cytochrome P450 2C9
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Wen X, Wang JS, Backman JT, Kivisto KT, Neuvonen PJ: Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos. 2001 Nov;29(11):1359-61. [PubMed:11602509]
  2. Tornio A, Niemi M, Neuvonen PJ, Backman JT: Stereoselective interaction between the CYP2C8 inhibitor gemfibrozil and racemic ibuprofen. Eur J Clin Pharmacol. 2007 May;63(5):463-9. doi: 10.1007/s00228-007-0273-9. Epub 2007 Feb 27. [PubMed:17333159]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data supported only by in vitro studies.
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wen X, Wang JS, Backman JT, Kivisto KT, Neuvonen PJ: Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos. 2001 Nov;29(11):1359-61. [PubMed:11602509]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Miller DB, Spence JD: Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet. 1998 Feb;34(2):155-62. doi: 10.2165/00003088-199834020-00003. [PubMed:9515185]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Gan J, Chen W, Shen H, Gao L, Hong Y, Tian Y, Li W, Zhang Y, Tang Y, Zhang H, Humphreys WG, Rodrigues AD: Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism. Br J Clin Pharmacol. 2010 Dec;70(6):870-80. doi: 10.1111/j.1365-2125.2010.03772.x. [PubMed:21175442]
  2. Williams JA, Hyland R, Jones BC, Smith DA, Hurst S, Goosen TC, Peterkin V, Koup JR, Ball SE: Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8. doi: 10.1124/dmd.104.000794. Epub 2004 Aug 10. [PubMed:15304429]
  3. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]
  4. FDA Label - ONIVYDE™ (irinotecan liposome injection) [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Gill KL, Houston JB, Galetin A: Characterization of in vitro glucuronidation clearance of a range of drugs in human kidney microsomes: comparison with liver and intestinal glucuronidation and impact of albumin. Drug Metab Dispos. 2012 Apr;40(4):825-35. doi: 10.1124/dmd.111.043984. Epub 2012 Jan 24. [PubMed:22275465]
  2. Gan J, Chen W, Shen H, Gao L, Hong Y, Tian Y, Li W, Zhang Y, Tang Y, Zhang H, Humphreys WG, Rodrigues AD: Repaglinide-gemfibrozil drug interaction: inhibition of repaglinide glucuronidation as a potential additional contributing mechanism. Br J Clin Pharmacol. 2010 Dec;70(6):870-80. doi: 10.1111/j.1365-2125.2010.03772.x. [PubMed:21175442]
  3. Hirvensalo P, Tornio A, Neuvonen M, Tapaninen T, Paile-Hyvarinen M, Karja V, Mannisto VT, Pihlajamaki J, Backman JT, Niemi M: Comprehensive Pharmacogenomic Study Reveals an Important Role of UGT1A3 in Montelukast Pharmacokinetics. Clin Pharmacol Ther. 2018 Jul;104(1):158-168. doi: 10.1002/cpt.891. Epub 2017 Nov 6. [PubMed:28940478]
  4. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]
  5. DRUG-DRUG INTERACTIONS – FROM KNOWLEDGE BASE TO CLINICAL IMPACT [File]
  6. The UDP-Glucuronosyltransferase 2B7 Isozyme Is Responsible for Gemfibrozil Glucuronidation in the Human Liver [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as...
Gene Name
UGT2B4
Uniprot ID
P06133
Uniprot Name
UDP-glucuronosyltransferase 2B4
Molecular Weight
60512.035 Da
References
  1. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. The major substrates of this isozyme are eugenol > 4-methylumbe...
Gene Name
UGT2B17
Uniprot ID
O75795
Uniprot Name
UDP-glucuronosyltransferase 2B17
Molecular Weight
61094.915 Da
References
  1. Mano Y, Usui T, Kamimura H: The UDP-glucuronosyltransferase 2B7 isozyme is responsible for gemfibrozil glucuronidation in the human liver. Drug Metab Dispos. 2007 Nov;35(11):2040-4. doi: 10.1124/dmd.107.017269. Epub 2007 Aug 1. [PubMed:17670842]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Sallustio BC, Fairchild BA, Pannall PR: Interaction of human serum albumin with the electrophilic metabolite 1-O-gemfibrozil-beta-D-glucuronide. Drug Metab Dispos. 1997 Jan;25(1):55-60. [PubMed:9010630]
  2. Hamberger C, Barre J, Zini R, Taiclet A, Houin G, Tillement JP: In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs. Int J Clin Pharmacol Res. 1986;6(6):441-9. [PubMed:3468088]

Drug created on June 13, 2005 07:24 / Updated on November 16, 2019 10:35