Drug/Small Molecule:

gemfibrozil

Overview

IUPAC Name:	5-(2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid
Trade Names:	Apo-Gemfibrozil; Bolutol; Cholespid; Decrelip; Fibratol; Fibrocit; Gemfibril; Gemfibromax; Gemlipid; Gen-Fibro; Genlip; Gevilon; Hipolixan; Jezil; Lipozid; Lipur; Lopid; Novo-Gemfibrozil; Nu-Gemfibrozil
PharmGKB Accession Id:	PA449750

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]

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.

ATC Therapeutic Category

• C10AB:Fibrates

Pharmacology and Interactions

Mechanism Of Action

Gemfibrozil increases the activity of extrahepatic lipoprotein lipase (LL), thereby increasing lipoprotein triglyceride lipolysis. 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.

Pharmacology

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).

Food Interactions

Take 30 minutes before meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Gemfibrozil mainly undergoes oxidation of a ring methyl group to successively form a hydroxymethyl and a carboxyl metabolite.

Protein Binding

95%

Absorption

Well absorbed from gastrointestinal tract (within 1-2 hours).

Half Life

1.5 hours

Toxicity

Oral, mouse: LD₅₀ = 3162 mg/kg. Symptoms of overdose include abdominal cramps, diarrhea, joint and muscle pain, nausea, and vomiting.

Chemical Properties

Chemical Formula:

C₁₅H₂₂O₃

SMILES Code:

CC1=CC(=C(C=C1)C)OCCCC(C)(C)C(=O)O

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

250.3334 / 250.1569

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	ABCB1	PD PK	Publications
	ACE	PD       GN	Publications
	APOE	PD       GN	Publications
	C3	PD       GN	Publications
	CYP2C8	PD PK	Publications
	CYP2C9	PD PK	Publications
	CYP3A4	PD PK	Publications
	ESRRA	PD       GN	Publications
	SLCO1B1	PD PK    GN	Publications
	SLCO2B1	PD PK FA	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Metabolizing Enzymes

• CYP3A4
• CYP2C9
• CYP2C8

Drug Targets

• LPL
• SLCO1B1
• PPARA

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	ezetimibe	PK	Publications
	repaglinide	PK	Publications
	warfarin		Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Cardiomyopathy, Dilated	PD PK FA	Publications
	Carotid Artery Diseases	PD PK	Publications
	Obesity	PD       GN	Publications
	Rhabdomyolysis	PD PK	Publications
	visceral obesity	PD       GN	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.