BEZAFIBRATE

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20ClNO4
Molecular Weight	361.819
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(OC1=CC=C(CCNC(=O)C2=CC=C(Cl)C=C2)C=C1)C(O)=O

InChI

InChIKey=IIBYAHWJQTYFKB-UHFFFAOYSA-N

InChI=1S/C19H20ClNO4/c1-19(2,18(23)24)25-16-9-3-13(4-10-16)11-12-21-17(22)14-5-7-15(20)8-6-14/h3-10H,11-12H2,1-2H3,(H,21,22)(H,23,24)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16168052
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/9171241 | https://www.ncbi.nlm.nih.gov/pubmed/24759758

Bezafibrate is a lipid-lowering fibric acid derivative. Bezafibrate directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. However, from a biochemical point of view, bezafibrate is a PPAR ligand with a relatively low potency. Bezafibrate leads to considerable raising of HDL cholesterol and reduces triglycerides, improves insulin sensitivity and reduces blood glucose level, significantly lowering the incidence of cardiovascular events and new diabetes in patients with features of metabolic syndrome. It is the only pan-PPAR activator with more than a quarter of a century of therapeutic experience with a good safety profile.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171241 \| https://www.ncbi.nlm.nih.gov/pubmed/24759758	Agonist 2752	37.37 µM [EC50]
Peroxisome proliferator-activated receptor delta 30 Target ID: CHEMBL3979 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171241 \| https://www.ncbi.nlm.nih.gov/pubmed/24759758	Agonist 2752	40.3 µM [EC50]
Peroxisome proliferator-activated receptor gamma 118 Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9171241 \| https://www.ncbi.nlm.nih.gov/pubmed/24759758	Agonist 2752	64.76 µM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperlipidemia 82 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3301301 https://www.ncbi.nlm.nih.gov/pubmed/18629356	Primary		Approved 8583	BEZALIP Approved Use Bezafibrate belongs to a group of medicines known as lipid-lowering substances.

C_max

Value	Dose	Analyte	Population
2.06 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=12	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.8 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=13	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
3.46 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=13	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3.75 μg/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=14	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
16.3 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
10.59 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/499297/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
8.02 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=12	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
7.41 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=13	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
13.27 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=13	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15.37 μg × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=14	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
256.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
154.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
69.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
3697 μg × h/dL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/499297/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.9 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=12	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=13	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2.3 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=13	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.3 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/340409_2183005G1099_1_003_1F.pdf#page=14	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
20.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
7.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
4.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7318880/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/499297/	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	BEZAFIBRATE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5.4% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/230034_2183005G1234_1_005_1F.pdf#page=20			BEZAFIBRATE serum	Homo sapiens
5% OTHER https://www.medicines.org.uk/emc/product/6547#PHARMACOKINETIC_PROPS			BEZAFIBRATE serum	Homo sapiens

Doses

Dose	Population	Adverse events
200 mg 1 times / day steady-state, oral Overdose Dose: 200 mg, 1 times / day Route: oral Route: steady-state Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	Disc. AE: Hemoglobin decreased, rhabdomyolysis... AEs leading to discontinuation/dose reduction: Hemoglobin decreased (1 pt) rhabdomyolysis (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/
400 mg 3 times / week multiple, oral Overdose Dose: 400 mg, 3 times / week Route: oral Route: multiple Dose: 400 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	Disc. AE: rhabdomyolysis, Hemoglobin decreased... AEs leading to discontinuation/dose reduction: rhabdomyolysis (1 pt) Hemoglobin decreased (1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/

AEs

AE	Significance	Dose	Population
Hemoglobin decreased	1 pt Disc. AE	200 mg 1 times / day steady-state, oral Overdose Dose: 200 mg, 1 times / day Route: oral Route: steady-state Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/
rhabdomyolysis	1 pt Disc. AE	200 mg 1 times / day steady-state, oral Overdose Dose: 200 mg, 1 times / day Route: oral Route: steady-state Dose: 200 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/
Hemoglobin decreased	1 pt Disc. AE	400 mg 3 times / week multiple, oral Overdose Dose: 400 mg, 3 times / week Route: oral Route: multiple Dose: 400 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/
rhabdomyolysis	1 pt Disc. AE	400 mg 3 times / week multiple, oral Overdose Dose: 400 mg, 3 times / week Route: oral Route: multiple Dose: 400 mg, 3 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/7870241/

PubMed

Title	Date	PubMed
[Clinical, epidemiologic, and biochemical findings on the reverse cholesterol transport (cholesterol-HDL)].	2001	11474568
Effects of diet, drugs, and genes on plasma fibrinogen levels.	2001	11460508
Bezafibrate-induced anaphylactic shock: unusual clinical presentation.	2001	11436973
Disorders of lipid metabolism in patients with HIV disease treated with antiretroviral agents: frequency, relationship with administered drugs, and role of hypolipidaemic therapy with bezafibrate.	2001 Apr	11545549
Effect of bezafibrate and clofibrate on the heme-iron geometry of ferrous nitrosylated heme-human serum albumin: an EPR study.	2001 Apr	11374593
Rhabdomyolysis and acute renal failure following a switchover of therapy between two fibric acid derivatives.	2001 Aug	11764054
Improvement in endothelial dysfunction in patients with hypoalphalipoproteinemia and coronary artery disease treated with bezafibrate.	2001 Aug	11483875
Bezafibrate reduces mRNA levels of adipocyte markers and increases fatty acid oxidation in primary culture of adipocytes.	2001 Aug	11473052
Concurrent administration of sustained-release bezafibrate may counteract the increased thrombotic risk associated with oral estrogen therapy.	2001 Aug	11461176
Effects of bezafibrate on beta-cell function of rat pancreatic islets.	2001 Aug 31	11527545
Alternations in hepatic expression of fatty-acid metabolizing enzymes in ArKO mice and their reversal by the treatment with 17beta-estradiol or a peroxisome proliferator.	2001 Dec	11850202
Lipid-lowering trials in diabetes.	2001 Dec	11801861
Alterations in the extrinsic pathway in hypertriglyceridemia do not cause a 'procoagulant state': effects of bezafibrate therapy.	2001 Dec	11734672
Blood lipids and first-ever ischemic stroke/transient ischemic attack in the Bezafibrate Infarction Prevention (BIP) Registry: high triglycerides constitute an independent risk factor.	2001 Dec 11	11739302
Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S.	2001 Dec 18	11748098
15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells.	2001 Dec 28	11687581
Oral antidiabetic treatment in patients with coronary disease: time-related increased mortality on combined glyburide/metformin therapy over a 7.7-year follow-up.	2001 Feb	11460818
[Fibrates in the secondary prevention of ischemic cardiopathy].	2001 Jan-Mar	11565320
Fibrate-induced increase in blood urea and creatinine.	2001 Jul	11427661
Treating dyslipidaemia in non-insulin-dependent diabetes mellitus -- a special reference to statins.	2001 Jul-Aug	11457674
Long-term diuretic therapy in patients with coronary disease: increased colon cancer-related mortality over a 5-year follow-up.	2001 Jun	11439311
Effect of bezafibrate in primary biliary cirrhosis: a pilot study.	2001 Jun	11422787
Normocholesterolaemic dysslipidaemia: is there a role for fibrates?	2001 Jun 4	11453341
Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.	2001 Mar	11579993
Effect of a pharmacological activation of PPAR on the expression of RAR and TR in rat liver.	2001 Mar	11519881
How is the liver primed or sensitized for alcoholic liver disease?	2001 May	11391068
Study of effectiveness of bezafibrate in the treatment of chronic hepatitis C.	2001 May	11374732
Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate.	2001 May	11372002
Effects of bezafibrate and simvastatin on plasma lipoproteins in hypercholesterolemia resistant to hormone replacement therapy.	2001 May 30	11358645
[Rhabdomyolysis and acute renal failure secondary to statins].	2001 May-Jun	11471312
Are high density lipoprotein (HDL) and triglyceride levels relevant in stroke prevention?	2001 Nov	11684067
Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats.	2001 Nov	11679425
High and low oxygen affinity conformations of T state hemoglobin.	2001 Nov	11604545
Squalene synthase inhibitors reduce plasma triglyceride through a low-density lipoprotein receptor-independent mechanism.	2001 Nov 23	11730728
Variation at position 162 of peroxisome proliferator-activated receptor alpha does not influence the effect of fibrates on cholesterol or triacylglycerol concentrations in hyperlipidaemic subjects.	2001 Oct	11668221
Antineoplastic and anti-inflammatory effects of PPAR ligands in colitis.	2001 Oct	11606520
A prospective study of plasma fibrinogen levels and the risk of stroke among participants in the bezafibrate infarction prevention study.	2001 Oct 15	11690571
Changes in matrix proteoglycans induced by insulin and fatty acids in hepatic cells may contribute to dyslipidemia of insulin resistance.	2001 Sep	11522680
Aromatase-deficient (ArKO) mice are retrieved from severe hepatic steatosis by peroxisome proliferator administration.	2002 Apr	11929713
Marked removal of bezafibrate-induced high-density lipoprotein-cholesterol by low-density lipoprotein apheresis.	2002 Apr	11880117
Soluble intercellular adhesion molecule-1 and long-term risk of acute coronary events in patients with chronic coronary heart disease. Data from the Bezafibrate Infarction Prevention (BIP) Study.	2002 Apr 3	11923036
[A case of primary sclerosing cholangitis presenting transient hypoperfusion and treated with bezafibrate beneficially].	2002 Feb	11877955
Use of fibrates in the management of hyperlipidemia in HIV-infected patients receiving HAART.	2002 Jan	11876511
Investigation into the efficacy of bezafibrate against primary biliary cirrhosis, with histological references from cases receiving long term monotherapy.	2002 Jan	11808959
Severity of angina pectoris and risk of ischemic stroke.	2002 Jan	11779917
Prevention of radiation-induced mammary tumors.	2002 Jan 1	11777641
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Evaluation of myopathy risk for HMG-CoA reductase inhibitors by urethane infusion method.	2002 Mar	11913531
Are high-density lipoprotein and triglyceride levels important in secondary prevention: impressions from the BIP and VA-HIT trials.	2002 Mar	11911905
Severe hypertriglyceridemia with insulin resistance is associated with systemic inflammation: reversal with bezafibrate therapy in a randomized controlled trial.	2002 Mar	11893366

Patents

Sample Use Guides

In Vivo Use Guide

Bezafibrate recommended dosage is 200 mg 3 times daily, or alternatively 400 mg once daily as a sustained-release preparation.

Route of Administration: Oral

In Vitro Use Guide

400 uM bezafibrate increases in the levels of carnitine palmitoyltransferase II activity, mitochondrial fatty acid β-oxidation, intracellular ATP, and mitochondrial membrane potential in human fibroblasts

Name

Type

Language

BEZAFIBRATE

Official Name

English

BEZATOL SR

Preferred Name

English

BM 15.075

Code

English

2-(P-(2-(P-CHLOROBENZAMIDO)ETHYL)PHENOXY)-2-METHYLPROPIONIC ACID

Common Name

English

BEZAFIBRATE [JAN]

Common Name

English

BEZAFIBRATE [USAN]

Common Name

English

BEZAFIBRATE [EP MONOGRAPH]

Common Name

English

Bezafibrate [WHO-DD]

Common Name

English

bezafibrate [INN]

Common Name

English

PROPANOIC ACID, 2-(4-(2-((4-CHLOROBENZOYL)AMINO)ETHYL)PHENOXY)-2-METHYL-

Common Name

English

BM-15075

Code

English

BM-15.075

Code

English

NSC-758174

Code

English

BEZAFIBRATE [MI]

Common Name

English

BEZAFIBRATE [MART.]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QC10AB02