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Identification
NameSimvastatin
Accession NumberDB00641  (APRD00104)
TypeSmall Molecule
GroupsApproved
Description

Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation of Aspergillus terreus. It is a 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
Synonyms
SynonymLanguageCode
2,2-Dimethylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8ar)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-oneNot AvailableNot Available
MK-733Not AvailableNot Available
SimvastatinNot AvailableNot Available
SimvastatinaSpanishNot Available
SimvastatineFrenchNot Available
SimvastatinumLatinNot Available
SynvinolinNot AvailableNot Available
ZocorNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
CholestatKalbe
ColeminBiohorm
LabistatinSandoz
LipexMerck Sharp & Dohme
LodalesSanofi-Aventis
MedipoMediolanum Farmaceutici
NivelipolTemis-Lostalo
SimovilMerck Sharp & Dohme
SinvacorMerck Sharp & Dohme
SivastinSigma-Tau
SivatinRowex
SivinarAnfarm
SorfoxGalex
SotovastinBros
StarezinLeovan Pharmaceuticals
StarstatLupin
StarzokoDaewoong
StasivaPharmanel
StatexPliva
StaticorDarnitsa
StatinalAlet Pharmaceuticals
StativerIapharm
ZocorMerck & Co
Brand mixtures
Brand NameIngredients
InegySimvastatin + Ezetimibe
JUVISYNCSimvastatin + Sitagliptin
SimcorNiacin + Simvastatin
VytorinSimvastatin + Ezetimibe
Categories
CAS number79902-63-9
WeightAverage: 418.5662
Monoisotopic: 418.271924326
Chemical FormulaC25H38O5
InChI KeyRYMZZMVNJRMUDD-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
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
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassLactones
SubclassDelta Valerolactones
Direct parentDelta Valerolactones
Alternative parentsOxanes; Dicarboxylic Acids and Derivatives; Secondary Alcohols; Carboxylic Acid Esters; Enolates; Polyamines; Ethers
Substituentsoxane; dicarboxylic acid derivative; secondary alcohol; carboxylic acid ester; carboxylic acid derivative; ether; polyamine; enolate; alcohol
Classification descriptionThis compound belongs to the delta valerolactones. These are cyclic organic compounds containing a 1-hydroxy-3,4,5,6-tetrahydro-1,2-thiazin-1- one moiety.
Pharmacology
IndicationFor the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart disease mortality and cardiovascular events. It can also be used in adolescent patients for the treatment of heterozygous familial hypercholesterolemia.
PharmacodynamicsSimvastatin, 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 actionSimvastatin is a prodrug in which 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.
AbsorptionAbsorption 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. However, because simvastatin undergoes extensive first-pass metabolism, the availability of the drug in the systemic is low. Peak plasma concentration occurs 1.3 - 2.4 hours after administration.
Volume of distribution

Simvastatin can cross the blood-brain-barrier.

Protein bindingBoth simvastatin and its β-hydroxyacid metabolite are highly bound (approximately 95%) to human plasma proteins.
Metabolism

Hepatic, simvastatin is a substrate for CYP3A4. The major active metabolites of simvastatin are β-hydroxyacid metabolite and its 6'-hydroxy, 6'-hydroxymethyl, and 6'-exomethylene derivatives

SubstrateEnzymesProduct
Simvastatin
simvastatin hydroxy acidDetails
Route of eliminationFollowing an oral dose of 14C-labeled simvastatin in man, 13% of the dose was excreted in urine and 60% in feces.
Half life3 hours
ClearanceNot Available
ToxicityThe most common adverse reactions that lead to discontinuation of therapy include gastrointestinal disorders (0.5%), myalgia (0.1%), and arthralgia (0.1%).
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Simvastatin Action PathwayDrug actionSMP00082
SNP Mediated Effects
Interacting Gene/EnzymeSNP RS IDAllele nameDefining changeEffectReference(s)
Kinesin-like protein KIF6
Gene symbol: KIF6
UniProt: Q6ZMV9
rs20455 Not AvailableC AlleleImproved response to statin drugs18222353
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Gene symbol: HMGCR
UniProt: P04035
rs17244841 Not AvailableT AlleleReduced response to statin drugs15199031
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9475
Blood Brain Barrier + 0.9422
Caco-2 permeable - 0.5951
P-glycoprotein substrate Substrate 0.8508
P-glycoprotein inhibitor I Inhibitor 0.7335
P-glycoprotein inhibitor II Inhibitor 0.8387
Renal organic cation transporter Non-inhibitor 0.8435
CYP450 2C9 substrate Non-substrate 0.835
CYP450 2D6 substrate Non-substrate 0.9254
CYP450 3A4 substrate Substrate 0.7513
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9307
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Inhibitor 0.7959
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8682
Ames test Non AMES toxic 0.792
Carcinogenicity Non-carcinogens 0.9408
Biodegradation Not ready biodegradable 0.9657
Rat acute toxicity 2.0061 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8921
hERG inhibition (predictor II) Non-inhibitor 0.8573
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
FormRouteStrength
TabletOral 5 mg, 10 mg, 20 mg, 40 mg, 80 mg
Prices
Unit descriptionCostUnit
Zocor 90 40 mg tablet Bottle525.16USDbottle
Simvastatin 100% powder10.71USDg
Vytorin 10-20 mg tablet5.05USDtablet
Vytorin 10-40 mg tablet5.05USDtablet
Vytorin 10-10 mg tablet4.97USDtablet
Zocor 20 mg tablet4.69USDtablet
Zocor 80 mg tablet4.69USDtablet
Vytorin 10-80 mg tablet4.63USDtablet
Zocor 40 mg tablet4.11USDtablet
Simvastatin 20 mg tablet3.83USDtablet
Simvastatin 40 mg tablet3.83USDtablet
Simvastatin 80 mg tablet3.83USDtablet
Zocor 10 mg tablet2.89USDtablet
Simvastatin 10 mg tablet2.31USDtablet
Zocor 5 mg tablet1.99USDtablet
Simvastatin 5 mg tablet1.63USDtablet
Phl-Simvastatin 40 mg Tablet1.45USDtablet
Phl-Simvastatin 80 mg Tablet1.45USDtablet
Pms-Simvastatin 20 mg Tablet1.45USDtablet
Pms-Simvastatin 40 mg Tablet1.45USDtablet
Pms-Simvastatin 80 mg Tablet1.45USDtablet
Ran-Simvastatin 20 mg Tablet1.45USDtablet
Ran-Simvastatin 40 mg Tablet1.45USDtablet
Ran-Simvastatin 80 mg Tablet1.45USDtablet
Ratio-Simvastatin 20 mg Tablet1.45USDtablet
Ratio-Simvastatin 40 mg Tablet1.45USDtablet
Ratio-Simvastatin 80 mg Tablet1.45USDtablet
Sandoz Simvastatin 20 mg Tablet1.45USDtablet
Sandoz Simvastatin 40 mg Tablet1.45USDtablet
Sandoz Simvastatin 80 mg Tablet1.45USDtablet
Apo-Simvastatin 20 mg Tablet1.45USDtablet
Apo-Simvastatin 40 mg Tablet1.45USDtablet
Apo-Simvastatin 80 mg Tablet1.45USDtablet
Co Simvastatin 20 mg Tablet1.45USDtablet
Co Simvastatin 40 mg Tablet1.45USDtablet
Co Simvastatin 80 mg Tablet1.45USDtablet
Jamp-Simvastatin 20 mg Tablet1.45USDtablet
Jamp-Simvastatin 40 mg Tablet1.45USDtablet
Jamp-Simvastatin 80 mg Tablet1.45USDtablet
Mylan-Simvastatin 20 mg Tablet1.45USDtablet
Mylan-Simvastatin 40 mg Tablet1.45USDtablet
Mylan-Simvastatin 80 mg Tablet1.45USDtablet
Novo-Simvastatin 20 mg Tablet1.45USDtablet
Novo-Simvastatin 40 mg Tablet1.45USDtablet
Novo-Simvastatin 80 mg Tablet1.45USDtablet
Phl-Simvastatin 20 mg Tablet1.45USDtablet
Apo-Simvastatin 10 mg Tablet1.17USDtablet
Co Simvastatin 10 mg Tablet1.17USDtablet
Jamp-Simvastatin 10 mg Tablet1.17USDtablet
Mylan-Simvastatin 10 mg Tablet1.17USDtablet
Novo-Simvastatin 10 mg Tablet1.17USDtablet
Phl-Simvastatin 10 mg Tablet1.17USDtablet
Pms-Simvastatin 10 mg Tablet1.17USDtablet
Ran-Simvastatin 10 mg Tablet1.17USDtablet
Ratio-Simvastatin 10 mg Tablet1.17USDtablet
Sandoz Simvastatin 10 mg Tablet1.17USDtablet
Apo-Simvastatin 5 mg Tablet0.59USDtablet
Co Simvastatin 5 mg Tablet0.59USDtablet
Jamp-Simvastatin 5 mg Tablet0.59USDtablet
Mylan-Simvastatin 5 mg Tablet0.59USDtablet
Novo-Simvastatin 5 mg Tablet0.59USDtablet
Phl-Simvastatin 5 mg Tablet0.59USDtablet
Pms-Simvastatin 5 mg Tablet0.59USDtablet
Ran-Simvastatin 5 mg Tablet0.59USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United StatesRE377211997-04-252017-04-25
United States58469661993-09-212013-09-21
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point135-138 °CPhysProp
water solubilityInsoluble FDA label
logP4.68HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0122ALOGPS
logP4.51ALOGPS
logP4.46ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)14.91ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.83 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity117.68 m3·mol-1ChemAxon
Polarizability47.85 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
References
Synthesis Reference

Shieh-Shung J. Chen, Byron H. Arison, “Process for the preparation of 3-keto, 5-hydroxy simvastatin analogs.” U.S. Patent US4965200, issued April, 1981.

US4965200
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
ResourceLink
KEGG DrugD00434
ChEBI9150
ChEMBLCHEMBL1064
Therapeutic Targets DatabaseDAP001519
PharmGKBPA451363
HETSIM
Drug Product Database2253747
RxListhttp://www.rxlist.com/cgi/generic/simva.htm
Drugs.comhttp://www.drugs.com/simvastatin.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zoc1500.shtml
WikipediaSimvastatin
ATC CodesC10AA01
AHFS Codes
  • 24:06.08
PDB EntriesNot Available
FDA labelshow(102 KB)
MSDSshow(87.5 KB)
Interactions
Drug Interactions
Drug
AmiodaroneIncreased risk of rhabdomyolysis
AmprenavirAmprenavir may increase the effect and toxicity of simvastatin. Concomitant therapy is contraindicated.
AtazanavirIncreased risk of myopathy/rhabdomyolysis
BosentanBosentan 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.
CarbamazepineCarbamazepine, 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.
ClarithromycinThe macrolide, clarithromycin, may increase the toxicity of the statin, simvastatin.
ColchicineIncreased risk of rhabdomyolysis with this combination
CyclosporinePossible myopathy and rhabdomyolysis
DelavirdineDelavirdine, 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.
DiltiazemDiltiazem 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.
DronedaroneDronedarone 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.
EfavirenzEfavirenz 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.
ErythromycinThe macrolide, erythromycin, may increase the toxicity of the statin, simvastatin.
EtravirineSimvastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of simvastatin therapy.
FenofibrateIncreased risk of myopathy/rhabdomyolysis
FluconazoleIncreased risk of myopathy/rhabdomyolysis
FosamprenavirFosamprenavir, 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 AcidIncreased risk of myopathy/rhabdomyolysis
GemfibrozilIncreased risk of myopathy/rhabdomyolysis
ImatinibImatinib, 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.
ItraconazoleIncreased risk of myopathy/rhabdomyolysis
KetoconazoleIncreased risk of myopathy/rhabdomyolysis
LomitapideSimvastatin plasma concentrations are doubled by lomitapide. To prevent dose related adverse effects such as myopathy and rhabdomyolysis it is recommended to reduce the dose of simvastatin by 50%. See FDA label for additional dosage instructions.
NefazodoneNefazodone 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.
NelfinavirNelfinavir may increase the effect and toxicity of simvastatin. Concomitant therapy should be avoided.
NevirapineThe 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.
PazopanibElevated liver enzyme levels may be observed with concomitant therapy with pazopanib. Monitor closely for adverse effects.
QuinupristinThis combination presents an increased risk of toxicity
RanolazineRanolazine 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.
RifabutinRifabutin 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.
RifampicinRifampin 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.
SaxagliptinSimvastatin 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.
TelaprevirTelaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
TelithromycinTelithromycin may increase the adverse effects of simvastatin by decreasing its metabolism. Concomitant therapy should be avoided.
TicagrelorPatients receiving more than 40 mg per day of simvastatin may be at increased risk of statin-related adverse effects.
TipranavirTipranavir, co-administered with Ritonavir, may increase the plasma concentration of Simvastatin. Concomitant therapy is contraindicated.
TocilizumabSimvastatin is a CYP3A4 and OATP1B1 substrate. Exposure of simvastatin decreases following administration of tocilizumab.
VerapamilVerapamil, 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.
VoriconazoleVoriconazole, 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

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
3-hydroxy-3-methylglutaryl-coenzyme A reductase P04035 Details

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

Kind: protein

Organism: Human

Pharmacological action: no

Actions: other

Components

Name UniProt ID Details
Integrin beta-2 P05107 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Cytochrome P450 3A7 P24462 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor inducer

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C19 P33261 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 2B6 P20813 Details

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

9. UDP-glucuronosyltransferase 1-1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-1 P22309 Details

References:

  1. http://www.pharmacologyweekly.com/content/pages/ugt-enzymes-medications-herbs-substrate-inhibitor-inducer

10. UDP-glucuronosyltransferase 1-3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-3 P35503 Details

References:

  1. http://www.pharmacologyweekly.com/content/pages/ugt-enzymes-medications-herbs-substrate-inhibitor-inducer

11. UDP-glucuronosyltransferase 2B7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 2B7 P16662 Details

References:

  1. http://www.pharmacologyweekly.com/content/pages/ugt-enzymes-medications-herbs-substrate-inhibitor-inducer

Transporters

1. Multidrug resistance protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Multidrug resistance protein 1 P08183 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B1 Q9Y6L6 Details

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

4. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Becker ML, Elens LL, Visser LE, Hofman A, Uitterlinden AG, van Schaik RH, Stricker BH: Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. Pharmacogenomics J. 2013 Jun;13(3):251-6. doi: 10.1038/tpj.2011.59. Epub 2011 Dec 20. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11