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Identification
NameLovastatin
Accession NumberDB00227  (APRD00370)
Typesmall molecule
Groupsapproved, investigational
Description

Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.

Structure
Thumb
Synonyms
SynonymLanguageCode
6-alpha-methylcompactinNot AvailableNot Available
6α-methylcompactinNot AvailableNot Available
LovastatinaSpanishNot Available
LovastatineFrenchNot Available
LovastatinumLatinNot Available
SaltsNot Available
Brand names
NameCompany
AltocorNot Available
AltoprevNot Available
MevacorMerck
Brand mixtures
Brand NameIngredients
Advicorniacin + lovastatin
Categories
CAS number75330-75-5
WeightAverage: 404.5396
Monoisotopic: 404.256274262
Chemical FormulaC24H36O5
InChI KeyPCZOHLXUXFIOCF-BXMDZJJMSA-N
InChI
InChI=1S/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,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 (2S)-2-methylbutanoate
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@@H](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 management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.
PharmacodynamicsThe primary cause of cardiovascular disease is atherosclerotic plaque formation. Sustained elevations of cholesterol in the blood increase the risk of cardiovascular disease. Lovastatin lowers hepatic cholesterol synthesis by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. At therapeutic doses, lovastatin decreases serum LDL cholesterol by 29-32%, increases high density lipoprotein (HDL) cholesterol by 4.6-7.3%, and decrease triglyceride levels by 2-12%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.
Mechanism of actionLovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring to form the β-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site.
AbsorptionStudies suggest that <5% of the oral dose reaches the general circulation as active inhibitors. Time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable.
Volume of distribution

Lovastatin is able to cross the blood-brain-barrier and placenta.

Protein bindingLovastatin and its β-hydroxyacid metabolites are highly protein bound (>95%).
Metabolism

Lovastatin is hepatically metabolized in which the major active metabolites are the β-hydroxyacid of lovastatin, the 6’-hydroxy derivative, and two additional metabolites.

Route of eliminationLovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. 83% of the orally administered dose is excreted in bile and 10% is excreted in urine.
Half life5.3 hours
ClearanceNot Available
ToxicityLD50>1000 mg/kg (orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Lovastatin Action PathwayDrug actionSMP00099
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9452
Blood Brain Barrier + 0.9287
Caco-2 permeable - 0.5484
P-glycoprotein substrate Substrate 0.7861
P-glycoprotein inhibitor I Inhibitor 0.7046
P-glycoprotein inhibitor II Inhibitor 0.8388
Renal organic cation transporter Non-inhibitor 0.8299
CYP450 2C9 substrate Non-substrate 0.8333
CYP450 2D6 substrate Non-substrate 0.9116
CYP450 3A4 substrate Substrate 0.6868
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9291
CYP450 2D6 substrate Non-inhibitor 0.923
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Inhibitor 0.796
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8682
Ames test Non AMES toxic 0.8475
Carcinogenicity Non-carcinogens 0.9519
Biodegradation Not ready biodegradable 0.8819
Rat acute toxicity 2.0554 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7272
hERG inhibition (predictor II) Non-inhibitor 0.7484
Pharmacoeconomics
Manufacturers
  • Andrx labs llc
  • Actavis elizabeth llc
  • Apotex inc
  • Carlsbad technology inc
  • Lupin ltd
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Merck research laboratories div merck co inc
Packagers
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral20 mg
TabletOral40 mg
Prices
Unit descriptionCostUnit
Altoprev 60 mg 24 Hour tablet7.99USDtablet
Altoprev 60 mg tablet7.74USDtablet
Altoprev 20 mg 24 Hour tablet6.88USDtablet
Altoprev 20 mg tablet6.61USDtablet
Mevacor 40 mg tablet4.57USDtablet
Altoprev 40 mg tablet4.41USDtablet
Lovastatin 40 mg tablet4.36USDtablet
Altoprev 10 mg 24 Hour tablet3.07USDtablet
Mevacor 20 mg tablet2.53USDtablet
Lovastatin 20 mg tablet2.42USDtablet
Altocor 20 mg 24 Hour tablet2.36USDtablet
Apo-Lovastatin 40 mg Tablet2.11USDtablet
Co Lovastatin 40 mg Tablet2.11USDtablet
Mylan-Lovastatin 40 mg Tablet2.11USDtablet
Novo-Lovastatin 40 mg Tablet2.11USDtablet
Pms-Lovastatin 40 mg Tablet2.11USDtablet
Ran-Lovastatin 40 mg Tablet2.11USDtablet
Ratio-Lovastatin 40 mg Tablet2.11USDtablet
Sandoz Lovastatin 40 mg Tablet2.11USDtablet
Mevacor 10 mg tablet1.65USDtablet
Lovastatin 10 mg tablet1.37USDtablet
Apo-Lovastatin 20 mg Tablet1.14USDtablet
Co Lovastatin 20 mg Tablet1.14USDtablet
Mylan-Lovastatin 20 mg Tablet1.14USDtablet
Novo-Lovastatin 20 mg Tablet1.14USDtablet
Pms-Lovastatin 20 mg Tablet1.14USDtablet
Ran-Lovastatin 20 mg Tablet1.14USDtablet
Ratio-Lovastatin 20 mg Tablet1.14USDtablet
Sandoz Lovastatin 20 mg Tablet1.14USDtablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States60807781998-03-232018-03-23
United States59165951997-12-122017-12-12
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point174.5 °CNot Available
water solubility0.0004 mg/mLNot Available
logP4.26HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
water solubility2.43e-02 g/lALOGPS
logP4.11ALOGPS
logP3.9ChemAxon
logS-4.2ALOGPS
pKa (strongest acidic)14.91ChemAxon
pKa (strongest basic)-2.8ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count3ChemAxon
hydrogen donor count1ChemAxon
polar surface area72.83ChemAxon
rotatable bond count7ChemAxon
refractivity113.18ChemAxon
polarizability46.11ChemAxon
number of rings3ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Donald F. Gerson, Xinfa Xiao, “Process for the production of lovastatin using Coniothyrium fuckelii.” U.S. Patent US5409820, issued January, 1984.

US5409820
General Reference
  1. Bobek P, Ozdin L, Galbavy S: Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998 Mar;14(3):282-6. Pubmed
External Links
ResourceLink
KEGG DrugD00359
KEGG CompoundC07074
PubChem Compound53232
PubChem Substance46508223
ChemSpider48085
ChEBI40303
ChEMBLCHEMBL503
Therapeutic Targets DatabaseDAP000551
PharmGKBPA450272
IUPHAR2739
Guide to Pharmacology2739
HET803
Drug Product Database2243127
RxListhttp://www.rxlist.com/cgi/generic3/altocor.htm
Drugs.comhttp://www.drugs.com/cdi/lovastatin.html
WikipediaLovastatin
ATC CodesC10AA02
AHFS Codes
  • 24:06.08
PDB EntriesNot Available
FDA labelshow(126 KB)
MSDSshow(99.6 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolLovastatin may increase the anticoagulant effect of acenocoumarol. Monitor for changes in the therapeutic and adverse effects of acenocoumarol if lovastatin is initiated, discontinued or dose changed.
AmprenavirAmprenavir may increase the serum concentration of the lovastatin. Concomitant therapy is contraindicated.
AnisindioneLovastatin may increase the anticoagulant effect of anisindione. Monitor for changes in the therapeutic and adverse effects of anisindione if lovastatin if initiated, discontinued or dose changed.
AtazanavirAtazanavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
AzithromycinThe macrolide antibiotic, azithromycin, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if azithromycin is initiated, discontinued or dose changed.
BezafibrateIncreased risk of myopathy/rhabdomyolysis
BosentanBosentan may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if bosentan is initiated, discontinued or dose changed.
CarbamazepineCarbamazepine, a p-glycoprotein inducer and strong CYP3A4 inducer, may decrease the effect of lovastatin by increasing its efflux and metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if carbamazepine is initiated, discontinued or dose changed.
ClarithromycinThe macrolide, clarithromycin, may increase the toxicity of the statin, lovastatin.
ColchicineIncreased risk of rhabdomyolysis with this combination
CyclosporinePossible myopathy and rhabdomyolysis
DanazolRisk of severe myopathy/rhabdomyolysis with this combination
DarunavirDarunavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
DelavirdineDelavirdine, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if delavirdine is initiated, discontinued or dose changed.
DicoumarolLovastatin may increase the anticoagulant effect dicumarol. Monitor for changes in the therapeutic and adverse effects of dicumarol if lovastatin is initiated, discontinued or dose changed.
DiltiazemDiltiazem may increase the serum concentration of lovastatin. Lovastatin 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.
EfavirenzEfavirenz may decrease the serum concentration of lovastatin by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if efavirenz is initiated, discontinued or dose changed.
ErythromycinThe macrolide, erythromycin, may increase the toxicity of the statin, lovastatin.
EtravirineLovastatin, when administered concomitantly with etravirine (a strong CYP3A4 inducer), may experience a decrease in serum concentration. It is recommended to monitor continued efficacy of lovastatin therapy.
FenofibrateIncreased risk of myopathy/rhabdomyolysis
FluconazoleIncreased risk of myopathy/rhabdomyolysis
FosamprenavirFosamprenavir, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Concomitant therapy is contraindicated.
GemfibrozilIncreased risk of myopathy/rhabdomyolysis
ImatinibImatinib, a strong CYP3A4 inhibitor, may increase the effect and toxicity of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if imatinib is initiated, discontinued or dose changed.
IndinavirIndinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
ItraconazoleIncreased risk of myopathy/rhabdomyolysis
JosamycinThe macrolide, josamycin, may increase the toxicity of the statin, lovastatin.
KetoconazoleIncreased risk of myopathy/rhabdomyolysis
LomitapideLovastatin plasma concentrations may increase by lomitapide.
NefazodoneNefazodone, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if nefazodone is initiated, discontinued or dose changed.
NelfinavirNelfinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
NevirapineThe strong CYP3A4 inducer, nevirapine, may decrase the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if nevirapine is initiated, discontinued or dose changed.
NiacinRisk of severe myopathy/rhabdomyolysis with this combination
QuinupristinThis combination presents an increased risk of toxicity
RifabutinRifabutin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifabutin is initiated, discontinued or dose changed.
RifampicinRifampin may decrease the effect of lovastatin by increasing its metabolism. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of lovastatin if rifampin is initiated, discontinued or dose changed.
RitonavirRitonavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
SaquinavirSaquinavir may increase the effect and toxicity of lovastatin. Concomitant therapy is contraindicated.
TelaprevirTelaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
TelithromycinTelithromycin may increase the adverse effects of lovastatin by decreasing its metabolism. Concomitant therapy should be avoided.
TicagrelorPatients receiving more than 40 mg per day of lovastatin may be at increased risk of statin-related adverse effects.
TipranavirTipranavir, co-administered with Ritonavir, may increase the plasma concentration of Lovastatin. Concomitant therapy is contraindicated.
VerapamilVerapamil, a moderate CYP3A4 inhibitor, may increase the serum concentration of Lovastatin 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 Lovastatin if Verapamil is initiated, discontinued or dose changed.
VoriconazoleVoriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of lovastatin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of lovastatin if voriconazole is initiated, discontinued or dose changed.
WarfarinLovastatin may increase the anticoagulant effect warfarin. Monitor for changes in the therapeutic and adverse effects of warfarin if lovastatin is initiated, discontinued or dose changed .
Food Interactions
  • Avoid alcohol.
  • Avoid drastic changes in dietary habit.
  • Avoid taking with grapefruit juice.
  • Take with food, 50% increase in bioavailability when taken with food.

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. Abe Y, Suzuki T, Ono C, Iwamoto K, Hosobuchi M, Yoshikawa H: Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster in Penicillium citrinum. Mol Genet Genomics. 2002 Jul;267(5):636-46. Epub 2002 Jun 28. Pubmed
  2. Miyazaki A, Koieyama T, Shimada Y, Kikuchi T, Nezu H, Ito K, Kasanuki N, Koga T: Effects of pravastatin sodium on mevalonate metabolism in common marmosets. J Biochem (Tokyo). 2002 Sep;132(3):395-400. Pubmed
  3. Buxbaum JD, Geoghagen NS, Friedhoff LT: Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide. J Alzheimers Dis. 2001 Apr;3(2):221-229. Pubmed
  4. Baranova NA, Kreier VG, Egorov NS: [Concentration on Diapak C 16 capsules of lovastatin, mevinolinic acid and other inhibitors of biosynthesis of sterins produced by Penicillium citrinum 89] Antibiot Khimioter. 2002;47(4):3-6. Pubmed
  5. Farina HG, Bublik DR, Alonso DF, Gomez DE: Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. Clin Exp Metastasis. 2002;19(6):551-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  7. Podar K, Tai YT, Hideshima T, Vallet S, Richardson PG, Anderson KC: Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. Pubmed
  8. Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P, Penn LZ, Kamel-Reid S: Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46. Pubmed

2. Integrin alpha-L

Kind: protein

Organism: Human

Pharmacological action: no

Actions: other/unknown

Components

Name UniProt ID Details
Integrin alpha-L P20701 Details

References:

  1. Kallen J, Welzenbach K, Ramage P, Geyl D, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U: Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol. 1999 Sep 10;292(1):1-9. Pubmed

3. Histone deacetylase 2

Kind: protein

Organism: Human

Pharmacological action: no

Actions: other

Components

Name UniProt ID Details
Histone deacetylase 2 Q92769 Details

References:

  1. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

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. Lexicomp

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. 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. Serum paraoxonase/lactonase 3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Serum paraoxonase/lactonase 3 Q15166 Details

References:

  1. Draganov DI, Stetson PL, Watson CE, Billecke SS, La Du BN: Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated lactonase and protects low density lipoprotein against oxidation. J Biol Chem. 2000 Oct 27;275(43):33435-42. Pubmed

5. Cytochrome P450 2C8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C8 P10632 Details

References:

  1. 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
  2. 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
  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 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. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  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. Lexicomp

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 2D6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: 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

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. Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, Pearson PG, Baillie TA: Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos. 2002 May;30(5):505-12. Pubmed

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. Kim RB, Wandel C, Leake B, Cvetkovic M, Fromm MF, Dempsey PJ, Roden MM, Belas F, Chaudhary AK, Roden DM, Wood AJ, Wilkinson GR: Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm Res. 1999 Mar;16(3):408-14. 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. Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB: OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine. Drug Metab Dispos. 1999 Aug;27(8):866-71. Pubmed
  2. 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: 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. Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB: Hepatic uptake of the novel antifungal agent caspofungin. Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16. 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. Ellis LC, Hawksworth GM, Weaver RJ: ATP-dependent transport of statins by human and rat MRP2/Mrp2. Toxicol Appl Pharmacol. 2013 Jun 1;269(2):187-94. doi: 10.1016/j.taap.2013.03.019. Epub 2013 Apr 2. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:08