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Identification
Name Gemfibrozil
Accession Number DB01241 (APRD00293)
Type small molecule
Groups approved
Description

A lipid-regulating agent that lowers elevated serum lipids primarily by decreasing serum triglycerides with a variable reduction in total cholesterol. These decreases occur primarily in the VLDL fraction and less frequently in the LDL fraction. Gemfibrozil increases HDL subfractions HDL2 and HDL3 as well as apolipoproteins A-I and A-II. Its mechanism of action has not been definitely established. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Brand names
  • Apo-Gemfibrozil
  • Bolutol
  • Cholespid
  • Decrelip
  • Fibratol
  • Fibrocit
  • Gemfibril
  • Gemfibromax
  • Gemlipid
  • Gen-Fibro
  • Genlip
  • Gevilon
  • Hipolixan
  • Jezil
  • Lipozid
  • Lipur
  • Lopid
  • Novo-Gemfibrozil
  • Nu-Gemfibrozil
Brand name mixtures Not Available
Categories
  • Antilipemic Agents
  • Fribic Acid Derivatives
CAS number 25812-30-0
Weight Average: 250.3334
Monoisotopic: 250.156894570
Chemical Formula C15H22O3
InChI Key InChIKey=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)
Plain Text
IUPAC Name
5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
SMILES
CC1=CC(OCCCC(C)(C)C(O)=O)=C(C)C=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbonyl Compounds
  • Phenols and Derivatives
  • Ethers
  • Anisoles
  • Phenyl Esters
Substructures
  • Carbonyl Compounds
  • Hydroxy Compounds
  • Acetates
  • Phenols and Derivatives
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Anisoles
  • Phenyl Esters
Pharmacology
Indication For treatment of adult patients with very high elevations of serum triglyceride levels (types IV and V hyperlipidemia) who are at risk of developing pancreatitis (inflammation of the pancreas) and who do not respond adequately to a strict diet.
Pharmacodynamics Gemfibrozil, a fibric acid antilipemic agent similar to clofibrate, is used to treat hyperlipoproteinemia and as a second-line therapy for type IIb hypercholesterolemia. It acts to reduce triglyceride levels, reduce VLDL levels, reduce LDL levels (moderately), and increase HDL levels (moderately).
Mechanism of action Gemfibrozil increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. It does so by activating Peroxisome proliferator-activated receptor-alpha (PPARĪ±) '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.
Absorption Well absorbed from gastrointestinal tract (within 1-2 hours).
Volume of distribution Not Available
Protein binding 95%
Metabolism

Hepatic. Gemfibrozil mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and a carboxyl metabolite.
Route of elimination Approximately seventy percent of the administered human dose is excreted in the urine, mostly as the glucuronide conjugate, with less than 2% excreted as unchanged gemfibrozil.
Half life 1.5 hours
Clearance Not Available
Toxicity Oral, mouse: LD50 = 3162 mg/kg. Symptoms of overdose include abdominal cramps, diarrhea, joint and muscle pain, nausea, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Pfizer pharmaceuticals ltd
  • Apotex inc
  • Dava pharmaceuticals inc
  • Impax pharmaceuticals
  • Invagen pharmaceuticals inc
  • Perrigo r and d co
  • Sandoz inc
  • Sun pharmaceutical industries inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral
Tablet Oral
Prices
Unit description Cost Unit
Gemfibrozil powder 2.88 USD g
Lopid 600 mg tablet 2.07 USD tablet
Gemfibrozil 600 mg tablet 1.8 USD tablet
Apo-Gemfibrozil 600 mg Tablet 0.65 USD tablet
Mylan-Gemfibrozil 600 mg Tablet 0.65 USD tablet
Novo-Gemfibrozil 600 mg Tablet 0.65 USD tablet
Nu-Gemfibrozil 600 mg Tablet 0.65 USD tablet
Pms-Gemfibrozil 600 mg Tablet 0.65 USD tablet
Lopid 300 mg Capsule 0.58 USD capsule
Apo-Gemfibrozil 300 mg Capsule 0.31 USD capsule
Mylan-Gemfibrozil 300 mg Capsule 0.31 USD capsule
Novo-Gemfibrozil 300 mg Capsule 0.31 USD capsule
Nu-Gemfibrozil 300 mg Capsule 0.31 USD capsule
Pms-Gemfibrozil 300 mg Capsule 0.31 USD capsule
Patents Not Available
Properties
State solid
Melting point 61-63 oC
Experimental Properties
Property Value Source
water solubility 10 mg/mL (in base) PhysProp
logP 3.4 PhysProp
Predicted Properties
Property Value Source
water solubility 2.78e-02 g/l ALOGPS
logP 3.61 ALOGPS
logP 4.39 ChemAxon Molconvert
logS -3.95 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 46.53 ChemAxon Molconvert
rotatable bond count 6 ChemAxon Molconvert
refractivity 71.82 ChemAxon Molconvert
polarizability 28.90 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00334 Link_out
PubChem Compound 3463 Link_out
PubChem Substance 46508264 Link_out
ChemSpider 3345 Link_out
ChEBI 5296 Link_out
ChEMBL 5296 Link_out
Therapeutic Targets Database DAP000210 Link_out
PharmGKB PA449750 Link_out
Drug Product Database 2241608 Link_out
RxList http://www.rxlist.com/cgi/generic/gemfib.htm Link_out
Drugs.com http://www.drugs.com/gemfibrozil.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lop1234.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Gemfibrozil Link_out
ATC Codes
  • C10AB04
AHFS Codes
  • 24:06.06
PDB Entries Not Available
FDA label show (260.4 KB)
MSDS show (74.3 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Take 30 minutes before meals.
Targets

1. Peroxisome proliferator-activated receptor alpha

Pharmacological action: yes
Actions: agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids

Organism class: human
UniProt ID: Q07869 Link_out
Gene: PPARA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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-cholesterol response of abdominally obese men treated with gemfibrozil. Genet Med. 2002 Jul-Aug;4(4):311-5. Pubmed
  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
  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
  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
Enzymes

1. Cytochrome P450 2C8

Actions: inhibitor, inducer

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2C19

Actions: inhibitor

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 imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Actions: inhibitor

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Solute carrier organic anion transporter family member 1B1

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:09

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.