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Identification
NameAtorvastatin
Accession NumberDB01076  (APRD00055)
Typesmall molecule
Groupsapproved
Description

Atorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.

Structure
Thumb
Synonyms
SynonymLanguageCode
LipovastatinklonalNot AvailableNot Available
Salts
Name/CAS Structure Properties
Atorvastatin Calcium
134523-03-8
Thumb
  • InChI Key: FQCKMBLVYCEXJB-ZUHSGPLBNA-L
  • Monoisotopic Mass: 1154.452941981
  • Average Mass: 1155.342
DBSALT000011
Brand names
NameCompany
AtogalIngers (Czech Republic)
CardylPfizer (Spain)
FaboximFabop (Argentina)
HipolixanPasteur (Chile)
LipitorPfizer, Elea (Argentina)
LipotropicDrugtech (Chile)
LiprimarPfizer (Hungary, Ukraine), Goedecke (Russia)
LowdenSaval (Chile)
NormalipQuesada (Argentina)
SincolIndeco (Argentina)
SortisPfizer (Austria, Czech Republic, Germany, Hungary, Poland, Portugal, Switzerland), Godecke (Germany), Parke, Davis (Germany)
TorvacardZentiva (Czech Republic, Hungary, Poland, Russia, Ukraine)
TorvastPfizer (Italy)
TotalipGuidotti (Italy)
TulipLek (Czech Republic, Russia), Wermar (Mexico), Sandoz (Poland, Ukraine), Pharmacia (Spain)
VastinaPenn (Argentina)
XanatorSieger (Greece)
XaratorParke, Davis (Italy)
ZurinelPrater (Chile)
Brand mixtures
Brand NameIngredients
Caduetatorvastatin calcium, amlodipine besilate
Liptruzet Atorvastatin calcium, ezetimibe
Categories
CAS number134523-00-5
WeightAverage: 557.6319
Monoisotopic: 557.245175413
Chemical FormulaC33H34FN2O5
InChI KeyXUKUURHRXDUEBC-UHFFFAOYNA-M
InChI
InChI=1/C33H35FN2O5/c1-21(2)31-30(33(41)35-25-11-7-4-8-12-25)29(22-9-5-3-6-10-22)32(23-13-15-24(34)16-14-23)36(31)18-17-26(37)19-27(38)20-28(39)40/h3-16,21,26-27,37-38H,17-20H2,1-2H3,(H,35,41)(H,39,40)/p-1
IUPAC Name
7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-(propan-2-yl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate
SMILES
CC(C)C1=C(C(=O)NC2=CC=CC=C2)C(=C(N1CCC(O)CC(O)CC([O-])=O)C1=CC=C(F)C=C1)C1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassPyrroles
SubclassSubstituted Pyrroles
Direct parentDiphenylpyrroles
Alternative parentsStilbenes; Anilides; Pyrrole Carboxamides; Heterocyclic Fatty Acids; Beta Hydroxy Acids and Derivatives; Fluorobenzenes; N-substituted Pyrroles; Aryl Fluorides; Secondary Carboxylic Acid Amides; Secondary Alcohols; Enolates; Carboxylic Acids; Polyamines; Organofluorides
Substituentsstilbene; acetanilide; pyrrole-3-carboxamide; pyrrole-3-carboxylic acid or derivative; fluorobenzene; beta-hydroxy acid; hydroxy acid; benzene; n-substituted pyrrole; aryl halide; aryl fluoride; carboxamide group; secondary alcohol; secondary carboxylic acid amide; polyamine; enolate; carboxylic acid; carboxylic acid derivative; alcohol; organonitrogen compound; amine; organohalogen; organofluoride
Classification descriptionThis compound belongs to the diphenylpyrroles. These are aromatic heterocyclic compounds whose structure is based on a pyrrole ring linked to exactly two phenyl groups.
Pharmacology
IndicationMay be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels.
PharmacodynamicsAtorvastatin, a selective, competitive HMG-CoA reductase inhibitor, is used to lower serum total and LDL cholesterol, apoB, and triglyceride levels while increasing HDL cholesterol. High LDL-C, low HDL-C and high TG concentrations in the plasma are associated with increased risk of atherosclerosis and cardiovascular disease. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Increased levels of HDL-C are associated with lower cardiovascular risk. By decreasing LDL-C and TG and increasing HDL-C, atorvastatin reduces the risk of cardiovascular morbidity and mortality. Atorvastatin has a unique structure, long half-life, and hepatic selectivity, explaining its greater LDL-lowering potency compared to other HMG-CoA reductase inhibitors.
Mechanism of actionAtorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
AbsorptionAtorvastatin is rapidly absorbed after oral administration with maximum plasma concentrations achieved in 1 to 2 hours. The absolute bioavailability of atorvastatin (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic bioavailability is due to presystemic clearance by gastrointestinal mucosa and first-pass metabolism in the liver.
Volume of distribution

381 L

Protein binding>98% bound to plasma proteins
Metabolism

Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. CYP3A4 is also involved in the metabolism of atorvastatin.

SubstrateEnzymesProduct
Atorvastatin
para-hydroxyatorvastatinDetails
Atorvastatin
ortho-hydroxyatorvastatinDetails
para-hydroxyatorvastatin
Not Available
para-hydroxyatorvastatin lactoneDetails
ortho-hydroxyatorvastatin
Not Available
ortho-hydroxyatorvastatin lactoneDetails
Atorvastatin
Not Available
Atorvastatin lactoneDetails
Route of eliminationEliminated primarily in bile after hepatic and/or extrahepatic metabolism. Does not appear to undergo significant enterohepatic recirculation. Less than 2% of the orally administered dose is recovered in urine.
Half life14 hours, but half-life of HMG-CoA inhibitor activity is 20-30 hours due to longer-lived active metabolites
ClearanceNot Available
ToxicityGenerally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
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
Multidrug resistance protein 1
Gene symbol: ABCB1
UniProt: P08183
rs1045642 MDR1*TT Allele (C3435T)Larger reduction in LDL and smaller increase in HDL cholesterol in females15081455
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8947
Blood Brain Barrier - 0.7825
Caco-2 permeable - 0.8956
P-glycoprotein substrate Substrate 0.5246
P-glycoprotein inhibitor I Inhibitor 0.7164
P-glycoprotein inhibitor II Inhibitor 0.8724
Renal organic cation transporter Non-inhibitor 0.8131
CYP450 2C9 substrate Non-substrate 0.7887
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6841
CYP450 1A2 substrate Non-inhibitor 0.8551
CYP450 2C9 substrate Non-inhibitor 0.719
CYP450 2D6 substrate Non-inhibitor 0.9042
CYP450 2C19 substrate Non-inhibitor 0.6191
CYP450 3A4 substrate Non-inhibitor 0.6675
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6894
Ames test Non AMES toxic 0.9133
Carcinogenicity Non-carcinogens 0.7777
Biodegradation Not ready biodegradable 0.9974
Rat acute toxicity 2.5686 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9904
hERG inhibition (predictor II) Non-inhibitor 0.5101
Pharmacoeconomics
Manufacturers
  • Pfizer inc
Packagers
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral20 mg
TabletOral40 mg
TabletOral80 mg
Prices
Unit descriptionCostUnit
Lipitor 20 mg tablet5.0USDtablet
Lipitor 40 mg tablet5.0USDtablet
Lipitor 80 mg tablet5.0USDtablet
Lipitor 10 mg tablet3.5USDtablet
Lipitor 40 mg Tablet2.52USDtablet
Lipitor 80 mg Tablet2.52USDtablet
Lipitor 20 mg Tablet2.34USDtablet
Lipitor 10 mg Tablet1.87USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States59691561997-01-082017-01-08
United States46818931992-09-242009-09-24
Canada25217762006-04-252022-05-21
Canada22200182001-04-172016-07-08
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point159.2-160.7 °CNot Available
water solubilitySodium salt soluble in water, 20.4 ug/mL (pH 2.1), 1.23 mg/mL (pH 6.0)Not Available
logP5.7Not Available
Predicted Properties
PropertyValueSource
water solubility4.95e-04 g/lALOGPS
logP4.41ALOGPS
logP5.39ChemAxon
logS-6.1ALOGPS
pKa (strongest acidic)4.33ChemAxon
pKa (strongest basic)-2.7ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area114.62ChemAxon
rotatable bond count12ChemAxon
refractivity169.04ChemAxon
polarizability59.7ChemAxon
number of rings4ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Zlatko Pflaum, “Process for the preparation of amorphous atorvastatin.” U.S. Patent US20020183527, issued December 05, 2002.

US20020183527
General Reference
  1. Rouleau J: Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial. Am J Med. 2005 Dec;118 Suppl 12A:28-35. Pubmed
  2. Maggon K: Best-selling human medicines 2002-2004. Drug Discov Today. 2005 Jun 1;10(11):739-42. Pubmed
  3. DailyMed FDA Label
External Links
ResourceLink
KEGG DrugD07474
KEGG CompoundC06834
BindingDB22164
ChEBI2910
ChEMBLCHEMBL1487
Therapeutic Targets DatabaseDAP000553
PharmGKBPA448500
HET117
Drug Product Database2243097
RxListhttp://www.rxlist.com/cgi/generic/atorvastatin.htm
Drugs.comhttp://www.drugs.com/atorvastatin.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/lip1230.shtml
WikipediaAtorvastatin
ATC CodesC10AA05
AHFS Codes
  • 24:06.08
PDB EntriesNot Available
FDA labelshow(62 KB)
MSDSshow(57.4 KB)
Interactions
Drug Interactions
Drug
AlvimopanDecreases levels by P-glycoprotein (MDR-1) efflux transporter. Can significantly increase systemic exposure to P-glycoprotein substrates.
AmprenavirAmprenavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
AtazanavirAtazanavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
BezafibrateIncreased risk of myopathy/rhabdomyolysis
BoceprevirBoceprevir increases the exposure of atorvastatin. Concomitant therapy should be closely monitored.
BosentanBosentan may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if bosentan is initiated, discontinued or dose changed.
CarbamazepineCarbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of atorvastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if carbamazepine is initiated, discontinued or dose changed.
ClarithromycinThe macrolide, clarithromycin, may increase the toxicity of the statin, atorvastatin.
ColchicineIncreased risk of rhadbomyolysis with this combination.
CyclosporinePossible myopathy and rhabdomyolysis
DelavirdineDelavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if delavirdine is initiated, discontinued or dose changed.
DiltiazemDiltiazem may increase the serum concentration of atorvastatin. Atorvastatin 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 atorvastatin. Lower doses of atorvastatin or consider rosuvastatin as cholesterol lowering therapy as there is no significant interaction between rosuvastatin and dronedarone.
EfavirenzEfavirenz may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if efavirenz is initiated, discontinued or dose changed.
EltrombopagEltrombopag increases levels of Atorvastatin via metabolism decrease.
ErythromycinThe macrolide, erythromycin, may increase the toxicity of the statin, atorvastatin.
EtravirineAtorvastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of atorvastatin therapy.
FenofibrateIncreased risk of myopathy/rhabdomyolysis
FluconazoleIncreased risk of myopathy/rhabdomyolysis
FosamprenavirFosamprenavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin 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 atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if imatinib is initiated, discontinued or dose changed.
IndinavirIndinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
ItraconazoleIncreased risk of myopathy/rhabdomyolysis
JosamycinThe macrolide, josamycin, may increase the toxicity of the statin, atorvastatin.
KetoconazoleIncreased risk of myopathy/rhabdomyolysis
LiraglutideThese agents may have decreased C max and a delayed T max during coadministration.
LomitapideAtorvastatin, and other weak CYP3A4 inhibitors (such as amiodarone, amlodipine, alprazolam, bicalutamide, cilostazol, cimetidine, cyclosporine, fluoxetine, fluvoxamine, ginko, goldenseal, isoniazide, lapatinib, nilotinib, oral contraceptives, pazopanib, ranitidine, ranolazine, tipranavir/ritonavir, ticagrelor, zileuton) increase lomitapide levels by 2-fold. Thus lomipatide should be dosed at a maximum of 30mg daily when used concomitantly with weak inhibitors of CYP3A4.
NefazodoneNefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nefazodone is initiated, discontinued or dose changed.
NelfinavirNelfinavir, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nelfinavir is initiated, discontinued or dose changed.
NevirapineNevirapine, a strong CYP3A4 inducer, may decrease the serum concentration of atorvastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if nevirapine is initiated, discontinued or dose changed.
QuinupristinThis combination presents an increased risk of toxicity
RifabutinRifabutin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifabutin is initiated, discontinued or dose changed.
RifampicinRifampin may decrease the effect of atorvastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if rifampin is initiated, discontinued or dose changed.
RitonavirRitonavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if ritonavir is initiated, discontinued or dose changed.
SaquinavirSaquinavir may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if saquinavir is initiated, discontinued or dose changed.
TelaprevirTelaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
TelithromycinThe macrolide antibiotic, telithromycin, may increase the serum concentration of atorvastatin by decreasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of atorvastatin if telithromycin is initiated, discontinued or dose changed.
TipranavirTipranavir, co-administered with Ritonavir, increases the adverse/toxic effects of Atorvastatin. Concomitant therapy should be avoided.
TopotecanThe p-glycoprotein inhibitor, Atorvastatin, may increase the bioavailability of oral Topotecan. A clinically significant effect is also expected with IV Topotecan. Concomitant therapy should be avoided.
VerapamilVerapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Atorvastatin by decreasing its metabolism. Avoid concurrent use if possible or reduce lovastatin dose during concomitant therapy. Monitor for changes in the therapeutic/adverse effects of Atorvastatin if Verapamil is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of atorvastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of atorvastatin if voriconazole is initiated, discontinued or dose changed.
Food Interactions
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid taking grapefruit or grapefruit juice throughout treatment. Grapefruit can significantly increase serum levels of this product.
  • Food may decrease maximum plasma levels and area under the curve, but this is clinically inconsequential according to the manufacturer.
  • Take with low fat meal.

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. Davidson MH: Rosuvastatin: a highly efficacious statin for the treatment of dyslipidaemia. Expert Opin Investig Drugs. 2002 Mar;11(3):125-41. Pubmed
  2. Jafari M, Ebrahimi R, Ahmadi-Kashani M, Balian H, Bashir M: Efficacy of alternate-day dosing versus daily dosing of atorvastatin. J Cardiovasc Pharmacol Ther. 2003 Jun;8(2):123-6. Pubmed
  3. Baxter JD, Webb P, Grover G, Scanlan TS: Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight. Trends Endocrinol Metab. 2004 May-Jun;15(4):154-7. Pubmed
  4. Maejima T, Yamazaki H, Aoki T, Tamaki T, Sato F, Kitahara M, Saito Y: Effect of pitavastatin on apolipoprotein A-I production in HepG2 cell. Biochem Biophys Res Commun. 2004 Nov 12;324(2):835-9. Pubmed
  5. Bosel J, Gandor F, Harms C, Synowitz M, Harms U, Djoufack PC, Megow D, Dirnagl U, Hortnagl H, Fink KB, Endres M: Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neurones. J Neurochem. 2005 Mar;92(6):1386-98. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Dipeptidyl peptidase 4

Kind: protein

Organism: Human

Pharmacological action: no

Actions: inhibitor

Components

Name UniProt ID Details
Dipeptidyl peptidase 4 P27487 Details

References:

  1. Taldone T, Zito SW, Talele TT: Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorg Med Chem Lett. 2008 Jan 15;18(2):479-84. Pubmed

3. Aryl hydrocarbon receptor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Aryl hydrocarbon receptor P35869 Details

References:

  1. Hu W, Sorrentino C, Denison MS, Kolaja K, Fielden MR: Induction of cyp1a1 is a nonspecific biomarker of aryl hydrocarbon receptor activation: results of large scale screening of pharmaceuticals and toxicants in vivo and in vitro. Mol Pharmacol. 2007 Jun;71(6):1475-86. Epub 2007 Feb 27. Pubmed
  2. Chauvin B, Drouot S, Barrail-Tran A, Taburet AM: Drug-Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors. Clin Pharmacokinet. 2013 May 24. Pubmed
  3. Chauvin B, Drouot S, Barrail-Tran A, Taburet AM: Drug-Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors. Clin Pharmacokinet. 2013 May 24. Pubmed
  4. Chauvin B, Drouot S, Barrail-Tran A, Taburet AM: Drug-Drug Interactions Between HMG-CoA Reductase Inhibitors (Statins) and Antiviral Protease Inhibitors. Clin Pharmacokinet. 2013 May 24. 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. 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. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. 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
  4. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. 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. 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
  2. Jacobsen W, Kuhn B, Soldner A, Kirchner G, Sewing KF, Kollman PA, Benet LZ, Christians U: Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos. 2000 Nov;28(11):1369-78. Pubmed

5. Cytochrome P450 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2D6 P10635 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

6. 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

7. 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

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. Stormo C, Bogsrud MP, Hermann M, Asberg A, Piehler AP, Retterstol K, Kringen MK: UGT1A1*28 is Associated with Decreased Systemic Exposure of Atorvastatin Lactone. Mol Diagn Ther. 2013 Apr 12. Pubmed

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. Stormo C, Bogsrud MP, Hermann M, Asberg A, Piehler AP, Retterstol K, Kringen MK: UGT1A1*28 is Associated with Decreased Systemic Exposure of Atorvastatin Lactone. Mol Diagn Ther. 2013 Apr 12. Pubmed

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. 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. Multidrug resistance-associated protein 4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 4 O15439 Details

References:

  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. Epub 2009 Nov 25. Pubmed

5. Multidrug resistance-associated protein 5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 5 O15440 Details

References:

  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. Epub 2009 Nov 25. Pubmed

6. Multidrug resistance-associated protein 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Multidrug resistance-associated protein 1 P33527 Details

References:

  1. Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG: Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010 Feb 5;106(2):297-306. Epub 2009 Nov 25. Pubmed

7. Solute carrier organic anion transporter family member 2B1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 2B1 O94956 Details

References:

  1. Grube M, Kock K, Oswald S, Draber K, Meissner K, Eckel L, Bohm M, Felix SB, Vogelgesang S, Jedlitschky G, Siegmund W, Warzok R, Kroemer HK: Organic anion transporting polypeptide 2B1 is a high-affinity transporter for atorvastatin and is expressed in the human heart. Clin Pharmacol Ther. 2006 Dec;80(6):607-20. Pubmed

8. Solute carrier organic anion transporter family member 1B3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1B3 Q9NPD5 Details

References:

  1. Klatt S, Fromm MF, Konig J: The influence of oral antidiabetic drugs on cellular drug uptake mediated by hepatic OATP family members. Basic Clin Pharmacol Toxicol. 2013 Apr;112(4):244-50. doi: 10.1111/bcpt.12031. Epub 2012 Dec 6. Pubmed

9. 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 October 12, 2013 12:55