Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C15H22O3 |
| Molecular Weight | 250.3334 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1
InChI
InChIKey=HEMJJKBWTPKOJG-UHFFFAOYSA-N
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)
DescriptionSources: http://www.drugbank.ca/drugs/DB01241Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018422s055lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB01241
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/018422s055lbl.pdf
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). 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. Gemfibrozil is most commonly sold as the brand name, Lopid. Other brand names include Jezil and Gen-Fibro.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22706077
Curator's Comment: gemfibrozil was shown to cross the blood brain barrier in mice
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1697668 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16316932 |
12.5 µM [Ki] | ||
Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16299161 |
30.0 µM [IC50] | ||
Target ID: CHEMBL3721 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16176562 |
30.4 µM [Ki] | ||
Target ID: CHEMBL239 Sources: http://www.drugbank.ca/drugs/DB01241 |
59.0 µM [EC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | LOPID Approved UseLOPID (gemfibrozil tablets, USP) is indicated as adjunctive therapy to diet for:
1. Treatment of adult patients with very high elevations of serum triglyceride levels (Types IV and V hyperlipidemia) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them.
2. Reducing the risk of developing coronary heart disease only in Type IIb patients without history of or symptoms of existing coronary heart disease who have had an inadequate response to weight loss, dietary therapy, exercise, and other pharmacologic agents (such as bile acid sequestrants and nicotinic acid, known to reduce LDL- and raise HDL-cholesterol) and who have the following triad of lipid abnormalities: low HDL-cholesterol levels in addition to elevated LDL-cholesterol
and elevated triglycerides Launch Date1981 |
|||
| Preventing | LOPID Approved UseLOPID (gemfibrozil tablets, USP) is indicated as adjunctive therapy to diet for:
1. Treatment of adult patients with very high elevations of serum triglyceride levels (Types IV and V hyperlipidemia) who present a risk of pancreatitis and who do not respond adequately to a determined dietary effort to control them.
2. Reducing the risk of developing coronary heart disease only in Type IIb patients without history of or symptoms of existing coronary heart disease who have had an inadequate response to weight loss, dietary therapy, exercise, and other pharmacologic agents (such as bile acid sequestrants and nicotinic acid, known to reduce LDL- and raise HDL-cholesterol) and who have the following triad of lipid abnormalities: low HDL-cholesterol levels in addition to elevated LDL-cholesterol
and elevated triglycerides Launch Date1981 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
17400 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT01736254 |
600 mg single, oral dose: 600 mg route of administration: oral experiment type: single co-administered: |
GEMFIBROZIL plasma | Homo sapiens population: healthy age: sex: food status: |
|
28 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19648824 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEMFIBROZIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
104 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19648824 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEMFIBROZIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
4.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19648824 |
600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEMFIBROZIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
Doses
| Dose | Population | Adverse events |
|---|---|---|
600 mg 2 times / day multiple, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, 59 |
Disc. AE: Depression, Flushing... AEs leading to discontinuation/dose reduction: Depression (1.1%) Sources: Flushing (1.1%) Nausea (2.2%) Vomiting (1.1%) Rash (1.1%) |
9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
Disc. AE: Abdominal cramps, Abnormal liver function tests... AEs leading to discontinuation/dose reduction: Abdominal cramps Sources: Abnormal liver function tests Diarrhea CPK increased Joint pain Muscle pain Nausea Vomiting |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Depression | 1.1% Disc. AE |
600 mg 2 times / day multiple, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, 59 |
| Flushing | 1.1% Disc. AE |
600 mg 2 times / day multiple, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, 59 |
| Rash | 1.1% Disc. AE |
600 mg 2 times / day multiple, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, 59 |
| Vomiting | 1.1% Disc. AE |
600 mg 2 times / day multiple, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, 59 |
| Nausea | 2.2% Disc. AE |
600 mg 2 times / day multiple, oral Recommended Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: |
unhealthy, 59 |
| Abdominal cramps | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| Abnormal liver function tests | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| CPK increased | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| Diarrhea | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| Joint pain | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| Muscle pain | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| Nausea | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
| Vomiting | Disc. AE | 9 g single, oral Overdose Dose: 9 g Route: oral Route: single Dose: 9 g Sources: |
healthy, 7 Health Status: healthy Age Group: 7 Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes [Ki 1.5 uM] | ||||
| yes [Ki 14.2 uM] | ||||
| yes [Ki 5.8 uM] | yes (co-administration study) Comment: [PMID:11719730]:Gemfibrozil modestly increases the plasma concentrations of glimepiride. This may be caused by inhibition of CYP2C9. |
|||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | yes (co-administration study) Comment: [PMID:22472994]: CYP2C8 inactivation by gemfibrozil caused dose-dependent increases in AUC of repaglinide |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| major | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes | ||||
| yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Hypercholesterolemia, lipid-lowering agents, and the risk for brain infarction. | 2001 |
|
| Hypertriglyceridemia: a review of clinical relevance and treatment options: focus on cerivastatin. | 2001 |
|
| Severe rhabdomyolysis associated with the cerivastin-gemfibrozil combination therapy: report of a case. | 2001 |
|
| Treatment of dyslipoproteinemia in the metabolic syndrome. | 2001 |
|
| Rhabdomyolysis after cerivastatin-gemfibrozil therapy in an HIV-infected patient with protease inhibitor-related hyperlipidemia. | 2001 Apr 13 |
|
| Rhabdomyolysis and acute renal failure following a switchover of therapy between two fibric acid derivatives. | 2001 Aug |
|
| [Fatal rhabdomyolysis caused by cerivastatin]. | 2001 Aug |
|
| Inhibitory action of gemfibrozil on cholesterol absorption in rat intestine. | 2001 Aug |
|
| Effect of a six month gemfibrozil treatment and dietary recommendations on the metabolic risk profile of visceral obese men. | 2001 Aug |
|
| Gemfibrozil treatment potentiates oxidative resistance of high-density lipoprotein in hypertriglyceridemic patients. | 2001 Aug |
|
| PPARalpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator. | 2001 Aug |
|
| A sensitive method for the determination of gemfibrozil in human plasma samples by RP-LC. | 2001 Aug |
|
| Bayer decides to withdraw cholesterol lowering drug. | 2001 Aug 18 |
|
| Baycol withdrawn from market. | 2001 Aug 21 |
|
| Altered expression of the carboxylesterases ES-4 and ES-10 by peroxisome proliferator chemicals. | 2001 Aug 28 |
|
| [Lipid-lowering drugs]. | 2001 Dec |
|
| Determination of drugs in surface water and wastewater samples by liquid chromatography-mass spectrometry: methods and preliminary results including toxicity studies with Vibrio fischeri. | 2001 Dec 14 |
|
| Targeting low high-density lipoprotein cholesterol for therapy: lessons from the Veterans Affairs High-density Lipoprotein Intervention Trial. | 2001 Dec 20 |
|
| [Fibrates in the secondary prevention of ischemic cardiopathy]. | 2001 Jan-Mar |
|
| Gemfibrozil prevents major coronary events by increasing HDL-cholesterol and more. | 2001 Jul |
|
| [Peroxisome proliferator-activated receptors (PPARs) in the vessel wall: new regulators of gene expression in vascular cells]. | 2001 Jul |
|
| Gemfibrozil improves insulin sensitivity and flow-mediated vasodilatation in type 2 diabetic patients. | 2001 Jul |
|
| Remnant-like lipoprotein particle cholesterol concentration and progression of coronary and vein-graft atherosclerosis in response to gemfibrozil treatment. | 2001 Jul |
|
| The effects of lipid-lowering agents on acute renal allograft rejection. | 2001 Jul 27 |
|
| Effects of fenofibrate and gemfibrozil on plasma homocysteine. | 2001 Jul 7 |
|
| Statin-fibrate combination therapy. | 2001 Jul-Aug |
|
| Combination therapy with cerivastatin and gemfibrozil causing rhabdomyolysis: is the interaction predictable? | 2001 Jun 1 |
|
| Normocholesterolaemic dysslipidaemia: is there a role for fibrates? | 2001 Jun 4 |
|
| Normocholesterolaemic dyslipidaemia: is there a role for fibrates? | 2001 Jun 4 |
|
| [Gemfibrozil: new aspects in clinical use]. | 2001 Mar |
|
| [VA-HIT Study [Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study]]. | 2001 Mar |
|
| Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study. | 2001 Nov |
|
| PPARS, metabolic disease and atherosclerosis. | 2001 Nov |
|
| Clinical inquiries. What laboratory monitoring is appropriate to detect adverse drug reactions in patients on cholesterol-lowering agents? | 2001 Nov |
|
| Statin-associated myopathy. | 2001 Nov 5 |
|
| Serum magnesium status during lipid-lowering drug treatment in non-insulin-dependent diabetic patients. | 2001 Oct |
|
| Cyclic nucleotides in platelets of genetically hypertriglyceridemic and hypertensive rats. Thrombin and nitric oxide responses are unrelated to plasma triglyceride levels. | 2001 Oct 1 |
|
| [Cerivastatin and gemfibrozil: a dangerous combination]. | 2001 Oct 15 |
|
| Molecular basis for the effect of lipid lowering drugs on growth factors after de-endothelialization. | 2001 Sep |
|
| [Cholestatic hepatitis caused by gemfibrozil]. | 2001 Sep |
|
| Cerivastatin and gemfibrozil-associated rhabdomyolysis. | 2001 Sep |
|
| Smoking diminishes the beneficial effect of statins: observations from the landmark trials. | 2001 Sep |
|
| Is the relationship between adipose tissue and waist girth altered by weight loss in obese men? | 2001 Sep |
|
| New developments in the prevention of atherosclerosis in patients with low high-density lipoprotein cholesterol. | 2001 Sep |
|
| [Severe rhabdomyolysis associated with cerivastatin and gemfibrozil]. | 2001 Sep 15 |
|
| Increase in hepatic expression of SREBP-2 by gemfibrozil administration to rats. | 2001 Sep 15 |
|
| Bayer pulls cerivastatin (Baycol) from market. | 2001 Sep 4 |
|
| [Rhabdomyolysis and anuric kidney failure induced by the treatment with a gemfibrozil-cerivastatin combination]. | 2001 Sep-Oct |
|
| Therapy and clinical trials. | 2002 Feb |
|
| Sexual dysfunction secondary to gemfibrozil. | 2002 Jan |
Sample Use Guides
The recommended dose for adults is 1200 mg administered in two divided doses 30 minutes before the morning and evening meals
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22285408
Sustained potent reduction of [Ca²⁺]i in cultured rat VSMCs was observed with Gemfibrozil 50mg/L
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| Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
834821
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FDA ORPHAN DRUG |
591917
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EU-Orphan Drug |
EU/3/18/1993
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NCI_THESAURUS |
C98150
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WHO-VATC |
QC10AB04
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FDA ORPHAN DRUG |
591917
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FDA ORPHAN DRUG |
546216
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NDF-RT |
N0000170118
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NDF-RT |
N0000175375
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NDF-RT |
N0000175596
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WHO-ATC |
C10AB04
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NDF-RT |
N0000170118
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LIVERTOX |
NBK547926
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FDA ORPHAN DRUG |
834921
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25812-30-0
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7735
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DB01241
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Q8X02027X3
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247-280-2
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3899
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100000092643
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DTXSID0020652
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SUB07894MIG
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Q8X02027X3
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1285
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757024
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3439
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4719
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D015248
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1288500
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Gemfibrozil
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C29071
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m5692
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CHEMBL457
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GEMFIBROZIL
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5296
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3463
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ACTIVE MOIETY
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)
METABOLITE (PARENT)