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Showing drug card for Cerivastatin (DB00439)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:03:39
Primary Accession Number DB00439
Secondary Accession Number
  • APRD00102
Name Cerivastatin
Drug Type
  • Small Molecule
  • Withdrawn
Description 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 It has also been withdrawn from the Canadian market.
Synonyms
  1. Cerivastatin sodium
  2. Cerivastatin, sodium salt
Brand Names
  1. Baycol
  2. Lipobay
  3. Rivastatin
Brand Mixtures Not Available
Chemical IUPAC Name (E,3R,5S)-7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-di(propan-2-yl)pyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid
Chemical Formula C26H34FNO5
Chemical Structure Structure
CAS Registry Number 145599-86-6
InChI Identifier InChI=1/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/f/h31H
InChI Key SEERZIQQUAZTOL-CMHQMAEVDV
KEGG Drug Not Available
KEGG Compound C07966 Link Image
PubChem Compound 446156 Link Image
PubChem Substance 206660 Link Image
ChEBI ID Not Available
PharmGKB ID PA448897 Link Image
HET ID 116 Link Image
GenBank ID Not Available
Drug ID Number [DIN] 02237325 Link Image
RxList Link http://www.rxlist.com/cgi/generic/cerivastat.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Cerivastatin Link Image
FDA Label
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Angerbauer R, Bischoff H, Steinke W and Ritter W (1994) BAY w 6228. Drugs Fut 19: 537-541.
Average Molecular Weight 459.5503
Monoisotopic Molecular Weight 459.2421
State Solid
Melting Point Not Available
Experimental Water Solubility Highly solubility Source: PhysProp
Predicted Water Solubility 4.19e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.4 Source: PhysProp
Predicted LogP 4.15 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -5.04 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric 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
Canonical SMILES COCC1=C(C2=CC=C(F)C=C2)C(C=CC(O)CC(O)CC(O)=O)=C(N=C1C(C)C)C(C)C
Drug Category
  • Anticholesteremic Agents
  • Antilipemic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
ATC Codes
AHFS Codes Not Available
Indication Used as an adjunct to diet for the reduction of elevated total and LDL cholesterol 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.
Pharmacology Cerivastatin, a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides, is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb).
Mechanism of Action Cerivastatin competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for converting HMG-CoA to mevalonate. As mevalonate is a precursor of sterols such as cholesterol, this results in a decrease in cholesterol in hepatic cells, upregulation of LDL-receptors, and an increase in hepatic uptake of LDL-cholesterol from the circulation.
Absorption The mean absolute oral bioavailability 60% (range 39 - 101%).
Toxicity Rhabdomyolysis, liver concerns
Protein Binding More than 99% of the circulating drug is bound to plasma proteins (80% to albumin).
Biotransformation Hepatic. Biotransformation pathways for cerivastatin in humans include the following: demethylation of the benzylic methyl ether to form Ml and hydroxylation of the methyl group in the 6'-isopropyl moiety to form M23.
Half Life 2-3 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Bezafibrate Increased risk of myopathy/rhabdomyolysis
Bosentan Bosentan could decrease the statin effect
Clarithromycin The macrolide possibly increases the statin toxicity
Colchicine Increased risk of rhabdomyolysis with this combination
Cyclosporine Possible myopathy and rhabdomyolysis
Diltiazem Diltiazem increases the effect and toxicity of the statin
Erythromycin The macrolide possibly increases the statin toxicity
Fenofibrate Increased risk of myopathy/rhabdomyolysis
Gemfibrozil Increased risk of myopathy/rhabdomyolysis
Imatinib Imatinib increases the effect and toxicity of statin
Itraconazole Increased risk of myopathy/rhabdomyolysis
Josamycin The macrolide possibly increases the statin toxicity
Ketoconazole Increased risk of myopathy/rhabdomyolysis
Nefazodone Nefazodone increases the effect and toxicity of the statin drug
Quinupristin This combination presents an increased risk of toxicity
Rifabutin The rifamycin decreases the effect of statin drug
Rifampin The rifamycin decreases the effect of statin drug
Food Interactions
  • Grapefruit and grapefruit juice should be avoided throughout treatment as grapefruit can significantly increase serum levels of this product.
  • Take without regard to meals.
Pathways
Name SMPDB Link KEGG Link
Cerivastatin Pathway SMP00111 Link Image
General References
  1. Furberg CD, Pitt B: Withdrawal of cerivastatin from the world market. Curr Control Trials Cardiovasc Med. 2001;2(5):205-207. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C8 (CYP2C8)
Targets
  1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C8 (CYP2C8)
Enzyme 1 Gene Name CYP2C8
Enzyme 1 SwissProt ID P10632 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P10632|CP2C8_HUMAN Cytochrome P450 2C8 (EC 1.14.14.1) 
MEPFVVLVLCLSFMLLFSLWRQSCRRRKLPPGPTPLPIIGNMLQIDVKDICKSFTNFSKV
YGPVFTVYFGMNPIVVFHGYEAVKEALIDNGEEFSGRGNSPISQRITKGLGIISSNGKRW
KEIRRFSLTTLRNFGMGKRSIEDRVQEEAHCLVEELRKTKASPCDPTFILGCAPCNVICS
VVFQKRFDYKDQNFLTLMKRFNENFRILNSPWIQVCNNFPLLIDCFPGTHNKVLKNVALT
RSYIREKVKEHQASLDVNNPRDFIDCFLIKMEQEKDNQKSEFNIENLVGTVADLFVAGTE
TTSTTLRYGLLLLLKHPEVTAKVQEEIDHVIGRHRSPCMQDRSHMPYTDAVVHEIQRYSD
LVPTGVPHAVTTDTKFRNYLIPKGTTIMALLTSVLHDDKEFPNPNIFDPGHFLDKNGNFK
KSDYFMPFSAGKRICAGEGLARMELFLFLTTILQNFNLKSVDDLKNLNTTAVTKGIVSLP
PSYQICFIPV
Drug Target 1 [top]
Target 1 ID 631
Target 1 Name 3-hydroxy-3-methylglutaryl-coenzyme A reductase
Target 1 Synonyms
  1. EC 1.1.1.34
  2. HMG-CoA reductase
Target 1 Gene Name HMGCR
Target 1 Protein Sequence >3-hydroxy-3-methylglutaryl-coenzyme A reductase 
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA
Target 1 Number of Residues 902
Target 1 Molecular Weight 97477
Target 1 Theoretical pI 6.72
Target 1 GO Classification
Function
hydroxymethylglutaryl-CoA reductase (NADPH) activity
hydroxymethylglutaryl-CoA reductase (NADPH) activity
catalytic activity
oxidoreductase activity
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
hydroxymethylglutaryl-CoA reductase (NADPH) activity
Process
primary metabolism
lipid metabolism
physiological process
metabolism
biosynthesis
Component
organelle membrane
endoplasmic reticulum membrane
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Lipid transport and metabolism
Target 1 Specific Function This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis
Target 1 Pathways
Name SMPDB Link KEGG Link
Biosynthesis of steroids map00100 Link Image
Target 1 Reactions
  • (R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H+
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 10-39
  • 57-78
  • 90-114
  • 124-149
  • 160-187
  • 192-220
  • 315-339
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 306865 Link Image
Target 1 UniProtKB/Swiss-Prot ID P04035 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name HMDH_HUMAN Link Image
Target 1 PDB ID 1HWL Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Endoplasmic reticulum
  • endoplasmic reticulum membrane
  • multi-pass membrane protein. Peroxisome
  • pero
Target 1 Gene Sequence >2667 bp 
ATGTTGTCAAGACTTTTTCGAATGCATGGCCTCTTTGTGGCCTCCCATCCCTGGGAAGTC
ATAGTGGGGACAGTGACACTGACCATCTGCATGATGTCCATGAACATGTTTACTGGTAAC
AATAAGATCTGTGGTTGGAATTATGAATGTCCAAAGTTTGAAGAGGATGTTTTGAGCAGT
GACATTATAATTCTGACAATAACACGATGCATAGCCATCCTGTATATTTACTTCCAGTTC
CAGAATTTACGTCAACTTGGATCAAAATATATTTTGGGTATTGCTGGCCTTTTCACAATT
TTCTCAAGTTTTGTATTCAGTACAGTTGTCATTCACTTCTTAGACAAAGAATTGACAGGC
TTGAATGAAGCTTTGCCCTTTTTCCTACTTTTGATTGACCTTTCCAGAGCAAGCACATTA
GCAAAGTTTGCCCTCAGTTCCAACTCACAGGATGAAGTAAGGGAAAATATTGCTCGTGGA
ATGGCAATTTTAGGTCCTACGTTTACCCTCGATGCTCTTGTTGAATGTCTTGTGATTGGA
GTTGGTACCATGTCAGGGGTACGTCAGCTTGAAATTATGTGCTGCTTTGGCTGCATGTCA
GTTCTTGCCAACTACTTCGTGTTCATGACTTTCTTCCCAGCTTGTGTGTCCTTGGTATTA
GAGCTTTCTCGGGAAAGCCGCGAGGGTCGTCCAATTTGGCAGCTCAGCCATTTTGCCCGA
GTTTTAGAAGAAGAAGAAAATAAGCCGAATCCTGTAACTCAGAGGGTCAAGATGATTATG
TCTCTAGGCTTGGTTCTTGTTCATGCTCACAGTCGCTGGATAGCTGATCCTTCTCCTCAA
AACAGTACAGCAGATACTTCTAAGGTTTCATTAGGACTGGATGAAAATGTGTCCAAGAGA
ATTGAACCAAGTGTTTCCCTCTGGCAGTTTTATCTCTCTAAAATGATCAGCATGGATATT
GAACAAGTTATTACCCTAAGTTTAGCTCTCCTTCTGGCTGTCAAGTACATCTTCTTTGAA
CAAACAGAGACAGAATCTACACTCTCATTAAAAAACCCTATCACATCTCCTGTAGTGACA
CAAAAGAAAGTCCCAGACAATTGTTGTAGACGTGAACCTATGCTGGTCAGAAATAACCAG
AAATGTGATTCAGTAGAGGAAGAGACAGGGATAAACCGAGAAAGAAAAGTTGAGGTTATA
AAACCCTTAGTGGCTGAAACAGATACCCCAAACAGAGCTACATTTGTGGTTGGTAACTCC
TCCTTACTCGATACTTCATCAGTACTGGTGACACAGGAACCTGAAATTGAACTTCCCAGG
GAACCTCGGCCTAATGAAGAATGTCTACAGATACTTGGGAATGCAGAGAAAGGTGCAAAA
TTCCTTAGTGATGCTGAGATCATCCAGTTAGTCAATGCTAAGCATATCCCAGCCTACAAG
TTGGAAACTCTGATGGAAACTCATGAGCGTGGTGTATCTATTCGCCGACAGTTACTTTCC
AAGAAGCTTTCAGAACCTTCTTCTCTCCAGTACCTACCTTACAGGGATTATAATTACTCC
TTGGTGATGGGAGCTTGTTGTGAGAATGTTATTGGATATATGCCCATCCCTGTTGGAGTG
GCAGGACCCCTTTGCTTAGATGAAAAAGAATTTCAGGTTCCAATGGCAACAACAGAAGGT
TGTCTTGTGGCCAGCACCAATAGAGGCTGCAGAGCAATAGGTCTTGGTGGAGGTGCCAGC
AGCCGAGTCCTTGCAGATGGGATGACTCGTGGCCCAGTTGTGCGTCTTCCACGTGCTTGT
GACTCTGCAGAAGTGAAAGCCTGGCTCGAAACATCTGAAGGGTTCGCAGTGATAAAGGAG
GCATTTGACAGCACTAGCAGATTTGCACGTCTACAGAAACTTCATACAAGTATAGCTGGA
CGCAACCTTTATATCCGTTTCCAGTCCAGGTCAGGGGATGCCATGGGGATGAACATGATT
TCAAAGGGTACAGAGAAAGCACTTTCAAAACTTCACGAGTATTTCCCTGAAATGCAGATT
CTAGCCGTTAGTGGTAACTATTGTACTGACAAGAAACCTGCTGCTATAAATTGGATAGAG
GGAAGAGGAAAATCTGTTGTTTGTGAAGCTGTCATTCCAGCCAAGGTTGTCAGAGAAGTA
TTAAAGACTACCACAGAGGCTATGATTGAGGTCAACATTAACAAGAATTTAGTGGGCTCT
GCCATGGCTGGGAGCATAGGAGGCTACAACGCCCATGCAGCAAACATTGTCACCGCCATC
TACATTGCCTGTGGACAGGATGCAGCACAGAATGTTGGTAGTTCAAACTGTATTACTTTA
ATGGAAGCAAGTGGTCCCACAAATGAAGATTTATATATCAGCTGCACCATGCCATCTATA
GAGATAGGAACGGTGGGTGGTGGGACCAACCTACTACCTCAGCAAGCCTGTTTGCAGATG
CTAGGTGTTCAAGGAGCATGCAAAGATAATCCTGGGGAAAATGCCCGGCAGCTTGCCCGA
ATTGTGTGTGGGACCGTAATGGCTGGGGAATTGTCACTTATGGCAGCATTGGCAGCAGGA
CATCTTGTCAAAAGTCACATGATTCACAACAGGTCGAAGATCAATTTACAAGACCTCCAA
GGAGCTTGCACCAAGAAGACAGCCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID HMGCR Link Image
Target 1 GenAtlas ID HMGCR Link Image
Target 1 HGNC ID HGNC:5006 Link Image
Target 1 Chromosome Location 5
Target 1 Locus 5q13.3-q14
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Istvan ES, Palnitkar M, Buchanan SK, Deisenhofer J: Crystal structure of the catalytic portion of human HMG-CoA reductase: insights into regulation of activity and catalysis. EMBO J. 2000 Mar 1;19(5):819-30. [PubMed Link Image]
  3. Luskey KL, Stevens B: Human 3-hydroxy-3-methylglutaryl coenzyme A reductase. Conserved domains responsible for catalytic activity and sterol-regulated degradation. J Biol Chem. 1985 Aug 25;260(18):10271-7. [PubMed Link Image]
Target 1 Drug References
  1. Shiomi M, Ito T: Effect of cerivastatin sodium, a new inhibitor of HMG-CoA reductase, on plasma lipid levels, progression of atherosclerosis, and the lesional composition in the plaques of WHHL rabbits. Br J Pharmacol. 1999 Feb;126(4):961-8. [PubMed Link Image]
  2. Blumenthal RS: Statins: effective antiatherosclerotic therapy. Am Heart J. 2000 Apr;139(4):577-83. [PubMed Link Image]
  3. Ganne F, Vasse M, Beaudeux JL, Peynet J, Francois A, Mishal Z, Chartier A, Tobelem G, Vannier JP, Soria J, Soria C: Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits urokinase/urokinase-receptor expression and MMP-9 secretion by peripheral blood monocytes--a possible protective mechanism against atherothrombosis. Thromb Haemost. 2000 Oct;84(4):680-8. [PubMed Link Image]
  4. Wong WW, Tan MM, Xia Z, Dimitroulakos J, Minden MD, Penn LZ: Cerivastatin triggers tumor-specific apoptosis with higher efficacy than lovastatin. Clin Cancer Res. 2001 Jul;7(7):2067-75. [PubMed Link Image]
  5. Denoyelle C, Vasse M, Korner M, Mishal Z, Ganne F, Vannier JP, Soria J, Soria C: Cerivastatin, an inhibitor of HMG-CoA reductase, inhibits the signaling pathways involved in the invasiveness and metastatic properties of highly invasive breast cancer cell lines: an in vitro study. Carcinogenesis. 2001 Aug;22(8):1139-48. [PubMed Link Image]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]

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.