CERIVASTATIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H34FNO5
Molecular Weight	459.5503
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COCC1=C(C2=CC=C(F)C=C2)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C(N=C1C(C)C)C(C)C

InChI

InChIKey=SEERZIQQUAZTOL-ANMDKAQQSA-N

InChI=1S/C26H34FNO5/c1-15(2)25-21(11-10-19(29)12-20(30)13-23(31)32)24(17-6-8-18(27)9-7-17)22(14-33-5)26(28-25)16(3)4/h6-11,15-16,19-20,29-30H,12-14H2,1-5H3,(H,31,32)/b11-10+/t19-,20-/m1/s1

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S19lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB00439

Cerivastatin (BAYCOL®) is a competitive inhibitor of HMG-CoA reductase, which is responsible for the conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) to mevalonate, a precursor of sterols, including cholesterol. The inhibition of cholesterol biosynthesis by cerivastatin reduces the level of cholesterol in hepatic cells, which stimulates the synthesis of low-density lipoprotein (LDL) receptors, thereby increasing the uptake of cellular LDL particles. The end result of these biochemical processes is a reduction of the plasma cholesterol concentration. On August 8, 2001 the U.S. Food and Drug Administration (FDA) announced that Bayer Pharmaceutical Division voluntarily withdrew BAYCOL® from the U.S. market, due to reports of fatal rhabdomyolysis, a severe adverse reaction from this cholesterol-lowering (lipid-lowering) product. It has also been withdrawn from the Canadian market.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
HMG-CoA reductase 47 Target ID: CHEMBL402 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S19lbl.pdf	Inhibitor 8297		5.7 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypercholesterolemia 47 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S19lbl.pdf	Primary		Withdrawn	BAYCOL Approved Use BAYCOL® (cerivastatin sodium tablets) is indicated as an adjunct to diet to reduce elevated Total-C, LDLC, apo B, and TG and to increase HDL-C levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate. Therapy with lipidaltering drugs should be a component of multiple risk factor intervention in those patients at significantly high risk for atherosclerotic vascular disease due to hypercholesterolemia Launch Date 8.6728317E11
Mixed dyslipidemia (Fredrickson types IIa and IIb) 2 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S19lbl.pdf	Primary		Withdrawn	BAYCOL Approved Use BAYCOL® (cerivastatin sodium tablets) is indicated as an adjunct to diet to reduce elevated Total-C, LDLC, apo B, and TG and to increase HDL-C levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate. Therapy with lipidaltering drugs should be a component of multiple risk factor intervention in those patients at significantly high risk for atherosclerotic vascular disease due to hypercholesterolemia Launch Date 8.6728317E11

C_max

Value	Dose	Analyte	Population
2.31 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	200 μg 1 times / day steady-state, oral dose: 200 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.96 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	300 μg 1 times / day steady-state, oral dose: 300 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.41 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	400 μg 1 times / day steady-state, oral dose: 400 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.14 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	100 μg 1 times / day steady-state, oral dose: 100 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
2.15 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	200 μg single, oral dose: 200 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.55 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	300 μg single, oral dose: 300 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.04 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	400 μg single, oral dose: 400 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
1.01 μg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
12.4 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	200 μg 1 times / day steady-state, oral dose: 200 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
21.73 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	300 μg 1 times / day steady-state, oral dose: 300 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
24.67 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	400 μg 1 times / day steady-state, oral dose: 400 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
6.33 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	100 μg 1 times / day steady-state, oral dose: 100 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
11.71 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	200 μg single, oral dose: 200 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
20.52 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	300 μg single, oral dose: 300 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
22.45 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	400 μg single, oral dose: 400 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
6.25 μg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
2.74 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	200 μg 1 times / day steady-state, oral dose: 200 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.79 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	300 μg 1 times / day steady-state, oral dose: 300 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
5.16 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	400 μg 1 times / day steady-state, oral dose: 400 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.19 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	100 μg 1 times / day steady-state, oral dose: 100 μg route of administration: Oral experiment type: STEADY-STATE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.08 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	200 μg single, oral dose: 200 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.89 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	300 μg single, oral dose: 300 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
4.23 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	400 μg single, oral dose: 400 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.37 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/nda/97/020740ap_baycol_clinphrmrp1.pdf	100 μg single, oral dose: 100 μg route of administration: Oral experiment type: SINGLE co-administered:	CERIVASTATIN SODIUM plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S19lbl.pdf	200 μg 1 times / day steady-state, oral dose: 200 μg route of administration: Oral experiment type: STEADY-STATE co-administered:		CERIVASTATIN SODIUM blood	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.8 mg 1 times / day steady, oral Studied dose Dose: 0.8 mg, 1 times / day Route: oral Route: steady Dose: 0.8 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10898118/	unhealthy, 57.2 years n = 776 Health Status: unhealthy Condition: hypercholesterolaemia Age Group: 57.2 years Sex: M+F Population Size: 776 Sources: https://pubmed.ncbi.nlm.nih.gov/10898118/	Disc. AE: CPK increased, Elevated liver enzymes... AEs leading to discontinuation/dose reduction: CPK increased (10 patients) Elevated liver enzymes (7 patients) Constipation (1 patient) Dyspepsia (1 patient) Flatulence (2 patients) Nausea (2 patients) Vomiting (2 patients) Chest pain (1 patient) Eye pain (1 patient) Head pain (1 patient) Leg pain (1 patient) Skin disorder (3 patients) Dizziness (2 patients) Insomnia (1 patient) Arthralgia (1 patient) Leg cramps (1 patient) Myalgia (3 patients) Myasthenia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10898118/
0.4 mg 1 times / day steady, oral Recommended Dose: 0.4 mg, 1 times / day Route: oral Route: steady Dose: 0.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10898118/	unhealthy, 57.3 years n = 195 Health Status: unhealthy Condition: hypercholesterolaemia Age Group: 57.3 years Sex: M+F Population Size: 195 Sources: https://pubmed.ncbi.nlm.nih.gov/10898118/	Disc. AE: CPK increased, Elevated liver enzymes... AEs leading to discontinuation/dose reduction: CPK increased (2 patients) Elevated liver enzymes (2 patients) Ulcerative colitis (1 patient) Headache (1 patient) Rash (2 patients) Exfoliative dermatitis (2 patients) Leg cramps (1 patient) Myalgia (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/10898118/
0.4 mg 1 times / day steady, oral Recommended Dose: 0.4 mg, 1 times / day Route: oral Route: steady Dose: 0.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11129127/	unhealthy, adult n = 1263 Health Status: unhealthy Condition: hypercholesterolaemia Age Group: adult Sex: unknown Population Size: 1263 Sources: https://pubmed.ncbi.nlm.nih.gov/11129127/	Disc. AE: Rhinitis, Headache... AEs leading to discontinuation/dose reduction: Rhinitis (2.8%) Headache (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/11129127/
0.4 mg 1 times / day steady, oral Recommended Dose: 0.4 mg, 1 times / day Route: oral Route: steady Dose: 0.4 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/11129127/	unhealthy, adult n = 2816 Health Status: unhealthy Condition: hypercholesterolaemia Age Group: adult Sex: unknown Population Size: 2816 Sources: https://pubmed.ncbi.nlm.nih.gov/11129127/	Disc. AE: Gastrointestinal disorders... AEs leading to discontinuation/dose reduction: Gastrointestinal disorders (3%) Sources: https://pubmed.ncbi.nlm.nih.gov/11129127/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
BCRP 699 OATP2B1 123 BSEP 402 CYP2C8 911	CYP2C8 693 P-gp 1537 OATP1B1 406

Drug as perpetrator

Target	Modality	Activity
CYP2C8 965	inhibitor 3277 Sources: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1742-7843.2005.pto_134.x	weak [IC50 30 uM]
OATP2B1 126	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17178262/	yes [IC50 66.2 uM]
BSEP 403	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/	yes [Ki 11.4 uM]
BCRP 773	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/15955871/	yes [Ki 18.1 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
OATP1B1 406	substrate 3367 Sources: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1755-5922.2011.00290.x	yes
P-gp 1537	substrate 3367 Sources: https://link.springer.com/article/10.1007/s00210-004-0948-z	yes
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S18lbl.pdf#page=2;https://pubmed.ncbi.nlm.nih.gov/15601807/ Page: 2.0	yes	yes (co-administration study) Comment: inhibition by gemfibrozil have shown an increase in cerivastatin plasma AUC values from 1.3- to 10-fold. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S18lbl.pdf#page=2;https://pubmed.ncbi.nlm.nih.gov/15601807/ Page: 2.0
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S18lbl.pdf#page=2 Page: 2.0	yes	yes (co-administration study) Comment: specific inhibition of the CYP 3A4 enzyme sub-class resulted in a 1.4- to 1.5-fold mean increase in cerivastatin plasma levels following cotreatment with erythromycin or itraconazole, possibly because of metabolism via the alternate CYP 2C8 pathway Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/20740S18lbl.pdf#page=2 Page: 2.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3559	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3559
MolPort	MolPort-003-845-726	https://www.molport.com/shop/molecule-link/MolPort-003-845-726
eMolecules	26944548	https://www.emolecules.com/cgi-bin/more?vid=26944548

PubMed

Title	Date	PubMed
Withdrawal of cerivastatin from the world market.	2001	11806796
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.	2001 Mar 8	11256847
Three-dimensional quantitative structure (3-D QSAR) activity relationship studies on imidazolyl and N-pyrrolyl heptenoates as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitors by comparative molecular similarity indices analysis (CoMSIA).	2005 Feb 15	15686906
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Binding thermodynamics of statins to HMG-CoA reductase.	2005 Sep 6	16128575

Patents

Sample Use Guides

In Vivo Use Guide

The starting-dose of BAYCOL® is 0.4 mg once daily in the evening regardless of previous lipid therapy. Since the maximal effect of cerivastatin is seen within 4 weeks lipid determinations should be performed at this time and the dose adjusted based upon patient response. Only patients requiring further lipid adjustment should be titrated to 0.8 mg. The dosage range is 0.2 mg to 0.8 mg. Cerivastatin may be taken with or without food.

Route of Administration: Oral

In Vitro Use Guide

Cerivastatin inhibited the membrane-bound (non-solubilized) 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase of the native microsomal fraction isolated from rat liver with a Ki value of 1.3 nM. Cerivastatin inhibited the cholesterol synthesis in the human hepatoma cell line HepG2 cells with a IC50 value of 1.0 nM.

Name

Type

Language

CERIVASTATIN

Official Name

English

CERIVASTATIN [HSDB]

Common Name

English

cerivastatin [INN]

Common Name

English

CERIVASTATIN [MI]

Common Name

English

Cerivastatin [WHO-DD]

Common Name

English

CERIVASTATIN [VANDF]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1655