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Identification
Name Simvastatin
Accession Number DB00641 (APRD00104)
Type small molecule
Groups approved
Description

A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (hydroxymethylglutaryl COA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL cholesterol. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Simvastatin [Usan:Ban:Inn]
Simvastatina [Spanish]
Simvastatine [French]
Simvastatinum [Latin]
Salts Not Available
Brand names
Name Company
Cholestat
Coledis
Colemin
Corolin
Denan
Labistatin
Lipex
Lodales
Medipo
Nivelipol
Pantok
Rendapid
Simovil
Sinvacor
Sivastin
Synvinolin
Vasotenal
Zocor
Zocord
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Brand mixtures
Brand Name Ingredients
Inegy Simvastatin + Ezetimibe
Vytorin Simvastatin + Ezetimibe
Categories
  • Anticholesteremic Agents
  • Antilipemic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
CAS number 79902-63-9
Weight Average: 418.5662
Monoisotopic: 418.271924326
Chemical Formula C25H38O5
InChI Key InChIKey=RYMZZMVNJRMUDD-HGQWONQESA-N
InChI
InChI=1S/C25H38O5/c1-6-25(4,5)24(28)30-21-12-15(2)11-17-8-7-16(3)20(23(17)21)10-9-19-13-18(26)14-22(27)29-19/h7-8,11,15-16,18-21,23,26H,6,9-10,12-14H2,1-5H3/t15-,16-,18+,19+,20-,21-,23-/m0/s1
Plain Text
IUPAC Name
(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate
SMILES
[H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]1C[C@@H](O)CC(=O)O1)OC(=O)C(C)(C)CC
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Not Available
Classes Not Available
Substructures Not Available
Pharmacology
Indication For the treatment of hypercholesterolemia.
Pharmacodynamics Simvastatin, the methylated form of lovastatin, is an oral antilipemic agent which inhibits HMG-CoA reductase. simvastatin is used in the treatment of primary hypercholesterolemia and is effective in reducing total and LDL-cholesterol as well as plasma triglycerides and apolipoprotein B.
Mechanism of action The 6-membered lactone ring of simvastatin is hydrolyzed in vivo to generate the beta,delta-dihydroxy acid, an active metabolite structurally similar to HMG-CoA (hydroxymethylglutaryl CoA). Once hydrolyzed, simvastatin competes with HMG-CoA for HMG-CoA reductase, a hepatic microsomal enzyme. Interference with the activity of this enzyme reduces the quantity of mevalonic acid, a precursor of cholesterol.
Absorption Absorption of simvastatin, estimated relative to an intravenous reference dose, in each of two animal species tested, averaged about 85% of an oral dose. In animal studies, after oral dosing, simvastatin achieved substantially higher concentrations in the liver than in non-target tissues.
Volume of distribution Not Available
Protein binding Both simvastatin and its b-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.
Metabolism Hepatic, simvastatin is a substrate for CYP3A4.
Route of elimination Following an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.
Half life 3 hours
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Synthon pharmaceuticals ltd
  • Accord healthcare inc
  • Aurobindo pharma ltd
  • Dr reddys laboratories inc
  • Dr reddys laboratories ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lupin ltd
  • Matrix laboratories ltd
  • Perrigo r and d co
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Watson laboratories inc
  • Zydus pharmaceuticals usa inc
  • Merck research laboratories div merck co inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Zocor 90 40 mg tablet Bottle 525.16 USD bottle
Simvastatin 100% powder 10.71 USD g
Vytorin 10-20 mg tablet 5.05 USD tablet
Vytorin 10-40 mg tablet 5.05 USD tablet
Vytorin 10-10 mg tablet 4.97 USD tablet
Zocor 20 mg tablet 4.69 USD tablet
Zocor 80 mg tablet 4.69 USD tablet
Vytorin 10-80 mg tablet 4.63 USD tablet
Zocor 40 mg tablet 4.11 USD tablet
Simvastatin 20 mg tablet 3.83 USD tablet
Simvastatin 40 mg tablet 3.83 USD tablet
Simvastatin 80 mg tablet 3.83 USD tablet
Zocor 10 mg tablet 2.89 USD tablet
Simvastatin 10 mg tablet 2.31 USD tablet
Zocor 5 mg tablet 1.99 USD tablet
Simvastatin 5 mg tablet 1.63 USD tablet
Phl-Simvastatin 40 mg Tablet 1.45 USD tablet
Phl-Simvastatin 80 mg Tablet 1.45 USD tablet
Pms-Simvastatin 20 mg Tablet 1.45 USD tablet
Pms-Simvastatin 40 mg Tablet 1.45 USD tablet
Pms-Simvastatin 80 mg Tablet 1.45 USD tablet
Ran-Simvastatin 20 mg Tablet 1.45 USD tablet
Ran-Simvastatin 40 mg Tablet 1.45 USD tablet
Ran-Simvastatin 80 mg Tablet 1.45 USD tablet
Ratio-Simvastatin 20 mg Tablet 1.45 USD tablet
Ratio-Simvastatin 40 mg Tablet 1.45 USD tablet
Ratio-Simvastatin 80 mg Tablet 1.45 USD tablet
Sandoz Simvastatin 20 mg Tablet 1.45 USD tablet
Sandoz Simvastatin 40 mg Tablet 1.45 USD tablet
Sandoz Simvastatin 80 mg Tablet 1.45 USD tablet
Apo-Simvastatin 20 mg Tablet 1.45 USD tablet
Apo-Simvastatin 40 mg Tablet 1.45 USD tablet
Apo-Simvastatin 80 mg Tablet 1.45 USD tablet
Co Simvastatin 20 mg Tablet 1.45 USD tablet
Co Simvastatin 40 mg Tablet 1.45 USD tablet
Co Simvastatin 80 mg Tablet 1.45 USD tablet
Jamp-Simvastatin 20 mg Tablet 1.45 USD tablet
Jamp-Simvastatin 40 mg Tablet 1.45 USD tablet
Jamp-Simvastatin 80 mg Tablet 1.45 USD tablet
Mylan-Simvastatin 20 mg Tablet 1.45 USD tablet
Mylan-Simvastatin 40 mg Tablet 1.45 USD tablet
Mylan-Simvastatin 80 mg Tablet 1.45 USD tablet
Novo-Simvastatin 20 mg Tablet 1.45 USD tablet
Novo-Simvastatin 40 mg Tablet 1.45 USD tablet
Novo-Simvastatin 80 mg Tablet 1.45 USD tablet
Phl-Simvastatin 20 mg Tablet 1.45 USD tablet
Apo-Simvastatin 10 mg Tablet 1.17 USD tablet
Co Simvastatin 10 mg Tablet 1.17 USD tablet
Jamp-Simvastatin 10 mg Tablet 1.17 USD tablet
Mylan-Simvastatin 10 mg Tablet 1.17 USD tablet
Novo-Simvastatin 10 mg Tablet 1.17 USD tablet
Phl-Simvastatin 10 mg Tablet 1.17 USD tablet
Pms-Simvastatin 10 mg Tablet 1.17 USD tablet
Ran-Simvastatin 10 mg Tablet 1.17 USD tablet
Ratio-Simvastatin 10 mg Tablet 1.17 USD tablet
Sandoz Simvastatin 10 mg Tablet 1.17 USD tablet
Apo-Simvastatin 5 mg Tablet 0.59 USD tablet
Co Simvastatin 5 mg Tablet 0.59 USD tablet
Jamp-Simvastatin 5 mg Tablet 0.59 USD tablet
Mylan-Simvastatin 5 mg Tablet 0.59 USD tablet
Novo-Simvastatin 5 mg Tablet 0.59 USD tablet
Phl-Simvastatin 5 mg Tablet 0.59 USD tablet
Pms-Simvastatin 5 mg Tablet 0.59 USD tablet
Ran-Simvastatin 5 mg Tablet 0.59 USD tablet
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DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States RE37721 1997-04-25 2017-04-25
United States 5846966 1993-09-21 2013-09-21
Properties
State solid
Experimental Properties
Property Value Source
melting point 135-138 °C PhysProp
water solubility 0.03 mg/L CHEN,XQ ET AL. (2002)
logP 4.68 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.22e-02 g/l ALOGPS
logP 4.51 ALOGPS
logP 4.46 ChemAxon
logS -4.5 ALOGPS
pKa (strongest acidic) 14.91 ChemAxon
pKa (strongest basic) -2.8 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 72.83 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 117.68 ChemAxon
polarizability 47.85 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Wolozin B, Wang SW, Li NC, Lee A, Lee TA, Kazis LE: Simvastatin is associated with a reduced incidence of dementia and Parkinson’s disease. BMC Med. 2007 Jul 19;5:20. Pubmed
External Links
Resource Link
KEGG Drug D00434 Link_out
ChEBI 9150 Link_out
ChEMBL 9150 Link_out
Therapeutic Targets Database DAP001519 Link_out
PharmGKB PA451363 Link_out
HET SIM Link_out
Drug Product Database 2253747 Link_out
RxList http://www.rxlist.com/cgi/generic/simva.htm Link_out
Drugs.com http://www.drugs.com/simvastatin.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zoc1500.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Simvastatin Link_out
ATC Codes
  • C10AA01
AHFS Codes
  • 24:06.08
PDB Entries Not Available
FDA label show (102 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amiodarone Increased risk of rhabdomyolysis
Amprenavir Amprenavir may increase the effect and toxicity of simvastatin. Concomitant therapy is contraindicated.
Atazanavir Increased risk of myopathy/rhabdomyolysis
Bosentan Bosentan may decrease the serum concentration of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if bosentan is initiated, discontinued or dose changed.
Carbamazepine Carbamazepine, a p-glycoprotein inducer, may decrease the effect of simvastatin by increasing its efflux. Monitor for changes in the therapeutic and adverse effects of simvastatin if carbamazepine is initiated, discontinued or dose changed.
Clarithromycin The macrolide, clarithromycin, may increase the toxicity of the statin, simvastatin.
Colchicine Increased risk of rhabdomyolysis with this combination
Cyclosporine Possible myopathy and rhabdomyolysis
Delavirdine Delavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if delavirdine is initiated, discontinued or dose changed.
Diltiazem Diltiazem may increase the serum concentration of simvastatin. Simvastatin may increase the serum concentration of diltiazem. Monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or if doses are changed.
Dronedarone Dronedarone is a CYP2D6 inhibitor thus increasing serum concentrations of simvastatin 4-fold. Lower doses of simvastatin and doses should not exceed 20 mg to avoid statin-induced toxicities like myopathy. Consider rosuvastatin as cholesterol lowering therapy as there is no significant interaction between rosuvastatin and dronedarone.
Efavirenz Efavirenz may decrease the serum concentration of simvastatin. Monitor for changes in the therapeutic and adverse effects of simvastatin if efavirenz is initiated, discontinued or dose changed.
Erythromycin The macrolide, erythromycin, may increase the toxicity of the statin, simvastatin.
Fenofibrate Increased risk of myopathy/rhabdomyolysis
Fluconazole Increased risk of myopathy/rhabdomyolysis
Fosamprenavir Fosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if fosamprenavir is initiated, discontinued or dose changed.
Fusidic Acid Increased risk of myopathy/rhabdomyolysis
Gemfibrozil Increased risk of myopathy/rhabdomyolysis
Imatinib Imatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if imatinib is initiated, discontinued or dose changed.
Itraconazole Increased risk of myopathy/rhabdomyolysis
Ketoconazole Increased risk of myopathy/rhabdomyolysis
Lomitapide Simvastatin plasma concentrations are doubled by lomitapide.
Nefazodone Nefazodone may increase the effect and toxicity of simvastatin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nefazodone is initiated, discontinued or dose changed.
Nelfinavir Nelfinavir may increase the effect and toxicity of simvastatin. Concomitant therapy should be avoided.
Nevirapine The strong CYP3A4 inducer, nevirapine, may decrase the effect of simvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of simvastatin if nevirapine is initiated, discontinued or dose changed.
Pazopanib Elevated liver enzyme levels may be observed with concomitant therapy with pazopanib. Monitor closely for adverse effects.
Quinupristin This combination presents an increased risk of toxicity
Ranolazine Ranolazine may increase the serum concentration of simvastatin. Monitor for changes in the therapeutic and adverse effects of simvastatin if ranolazine is initiated, discontinued or dose changed.
Rifabutin Rifabutin may decrease the effect of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic effect of simvastatin if rifabutin is initiated, discontinued or dose changed.
Rifampin Rifampin may decrease the effect of simvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastatin if rifampin is initiated, discontinued or dose changed.
Saxagliptin Simvastatin is a moderate inhibitor of CYP3A4 and increases AUC of saxagliptin by 12%. Exposure of the active metabolite decreased by 2%. However, these changes in pharmacokinetics are not clinical significant.
Telithromycin Telithromycin may increase the adverse effects of simvastatin by decreasing its metabolism. Concomitant therapy should be avoided.
Ticagrelor Patients receiving more than 40 mg per day of simvastatin may be at increased risk of statin-related adverse effects.
Tipranavir Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Simvastatin. Concomitant therapy is contraindicated.
Verapamil Verapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Simvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce Simvastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Simvastatin if Verapamil is initiated, discontinued or dose changed.
Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of simvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of simvastain if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid taking with grapefruit juice.
Targets

1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase

Pharmacological action: yes
Actions: inhibitor

This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis

Organism class: human
UniProt ID: P04035 Link_out
Gene: HMGCR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cenedella RJ, Kuszak JR, Al-Ghoul KJ, Qin S, Sexton PS: Discordant expression of the sterol pathway in lens underlies simvastatin-induced cataracts in Chbb: Thom rats. J Lipid Res. 2003 Jan;44(1):198-211. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Kocarek TA, Dahn MS, Cai H, Strom SC, Mercer-Haines NA: Regulation of CYP2B6 and CYP3A expression by hydroxymethylglutaryl coenzyme A inhibitors in primary cultured human hepatocytes. Drug Metab Dispos. 2002 Dec;30(12):1400-5. Pubmed
  4. Liu L, Zhang R, Zhao JJ, Rogers JD, Hsieh JY, Fang W, Matuszewski BK, Dobrinska MR: Determination of simvastatin-derived HMG-CoA reductase inhibitors in biomatrices using an automated enzyme inhibition assay with radioactivity detection. J Pharm Biomed Anal. 2003 Apr 24;32(1):107-23. Pubmed
  5. Pappu AS, Bacon SP, Illingworth DR: Residual effects of lovastatin and simvastatin on urinary mevalonate excretions in patients with familial hypercholesterolemia. J Lab Clin Med. 2003 Apr;141(4):250-6. Pubmed
  6. Stoebner PE, Michot C, Ligeron C, Durand L, Meynadier J, Meunier L: [Simvastatin-induced lichen planus pemphigoides] Ann Dermatol Venereol. 2003 Feb;130(2 Pt 1):187-90. Pubmed

2. Integrin beta-2

Pharmacological action: no
Actions: other

Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. Integrins alpha-M/beta-2 and alpha-X/beta-2 are receptors for the iC3b fragment of the third complement component and for fibrinogen. Integrin alpha-X/beta-2 recognizes the sequence G-P-R in fibrinogen alpha-chain. Integrin alpha-M/beta-2 recognizes P1 and P2 peptides of fibrinogen gamma chain. Integrin alpha-M/beta-2 is also a receptor for factor X. Integrin alpha- D/beta-2 is a receptor for ICAM3 and VCAM1

Organism class: human
UniProt ID: P05107 Link_out
Gene: ITGB2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Fujii T, Masuyama K, Kawashima K: Simvastatin regulates non-neuronal cholinergic activity in T lymphocytes via CD11a-mediated pathways. J Neuroimmunol. 2006 Oct;179(1-2):101-7. Epub 2006 Jul 10. Pubmed
  2. Fujii T, Takada-Takatori Y, Kawashima K: Roles played by lymphocyte function-associated antigen-1 in the regulation of lymphocytic cholinergic activity. Life Sci. 2007 May 30;80(24-25):2320-4. Epub 2007 Jan 17. Pubmed
  3. Katano H, Pesnicak L, Cohen JI: Simvastatin induces apoptosis of Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines and delays development of EBV lymphomas. Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):4960-5. Epub 2004 Mar 23. Pubmed
  4. Takahashi HK, Mori S, Iwagaki H, Yoshino T, Tanaka N, Nishibori M: Simvastatin induces interleukin-18 production in human peripheral blood mononuclear cells. Clin Immunol. 2005 Sep;116(3):211-6. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. Pubmed
  2. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  5. Information Hyperlinked Over Proteins (iHOP) – Website
  6. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  7. Galetin A, Clarke SE, Houston JB: Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos. 2002 Dec;30(12):1512-22. Pubmed

2. Cytochrome P450 3A5

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

4. Cytochrome P450 2C8

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol)

UniProt ID: P10632 Link_out
Gene: CYP2C8
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Neuvonen PJ, Niemi M, Backman JT: Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther. 2006 Dec;80(6):565-81. Pubmed
  2. Tornio A, Pasanen MK, Laitila J, Neuvonen PJ, Backman JT: Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8. Basic Clin Pharmacol Toxicol. 2005 Aug;97(2):104-8. Pubmed
  3. Walsky RL, Gaman EA, Obach RS: Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78. Pubmed
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

5. Cytochrome P450 2C9

Actions: inhibitor, inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

6. Cytochrome P450 2C19

Actions: inhibitor

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cohen LH, van Leeuwen RE, van Thiel GC, van Pelt JF, Yap SH: Equally potent inhibitors of cholesterol synthesis in human hepatocytes have distinguishable effects on different cytochrome P450 enzymes. Biopharm Drug Dispos. 2000 Dec;21(9):353-64. Pubmed

7. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

8. Cytochrome P450 2B6

Actions: inducer

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20813 Link_out
Gene: CYP2B6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wang E, Casciano CN, Clement RP, Johnson WW: HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharm Res. 2001 Jun;18(6):800-6. Pubmed
  2. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. Pubmed
  3. Hochman JH, Pudvah N, Qiu J, Yamazaki M, Tang C, Lin JH, Prueksaritanont T: Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharm Res. 2004 Sep;21(9):1686-91. Pubmed
  4. Sieczkowski E, Lehner C, Ambros PF, Hohenegger M: Double impact on p-glycoprotein by statins enhances doxorubicin cytotoxicity in human neuroblastoma cells. Int J Cancer. 2010 May 1;126(9):2025-35. Pubmed

2. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity)

UniProt ID: P46721 Link_out
Gene: SLCO1A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. Pubmed

3. Solute carrier organic anion transporter family member 1B1

Actions: substrate, inhibitor

Mediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver

UniProt ID: Q9Y6L6 Link_out
Gene: SLCO1B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hsiang B, Zhu Y, Wang Z, Wu Y, Sasseville V, Yang WP, Kirchgessner TG: A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999 Dec 24;274(52):37161-8. Pubmed
  2. Kameyama Y, Yamashita K, Kobayashi K, Hosokawa M, Chiba K: Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells. Pharmacogenet Genomics. 2005 Jul;15(7):513-22. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19