Identification

Name
Fluvastatin
Accession Number
DB01095  (APRD00346)
Type
Small Molecule
Groups
Approved
Description

Fluvastatin is an antilipemic agent that competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonic acid, the rate-limiting step in cholesterol biosynthesis. Fluvastatin belongs to a class of medications called statins and is used to reduce plasma cholesterol levels and prevent cardiovascular disease. It is also the first entirely synthetic HMG-CoA reductase inhibitor and is structurally distinct from the fungal derivatives of this therapeutic class. Fluvastatin is a racemate comprising equimolar amounts of (3R,5S)- and (3S,5R)-fluvastatin.

Structure
Thumb
Synonyms
  • fluvastatina
  • fluvastatine
  • fluvastatinum
Product Ingredients
IngredientUNIICASInChI Key
Fluvastatin sodiumPYF7O1FV7F93957-55-2ZGGHKIMDNBDHJB-NRFPMOEYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
LescolCapsule40 mg/1OralNovartis Pharmaceuticals Corporation2007-01-092007-01-09Us
LescolCapsule20 mg/1OralNovartis Pharmaceuticals Corporation2007-01-092007-01-09Us00078 0176 15 nlmimage10 b80edc36
LescolCapsule40 mg/1OralPhysicians Total Care, Inc.2002-03-08Not applicableUs
LescolCapsule20 mg/1OralPhysicians Total Care, Inc.1994-06-10Not applicableUs54868 332920180907 15195 4kz9nn
Lescol 20mgCapsule20 mgOralNovartis1994-12-31Not applicableCanada
Lescol 40mgCapsule40 mgOralNovartis1994-12-31Not applicableCanada
Lescol XLTablet, extended release80 mg/1OralCarilion Materials Management2000-10-06Not applicableUs68151 447120180907 15195 1eeux1x
Lescol XLTablet, extended release80 mg/1OralPhysicians Total Care, Inc.2002-03-12Not applicableUs54868 460120180907 15195 1b1tffw
Lescol XLTablet, extended release80 mgOralNovartis2004-04-05Not applicableCanada
Lescol XLTablet, extended release80 mg/1OralNovartis2000-10-06Not applicableUs00078 0354 05 nlmimage10 37091bf8
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
FluvastatinCapsule40 mg/1OralTeva Pharmaceuticals USA, Inc.2012-07-05Not applicableUs00093 7443 56 nlmimage10 052702b8
FluvastatinCapsule20 mg/1OralTeva Pharmaceuticals USA, Inc.2012-07-05Not applicableUs00093 7442 56 nlmimage10 30271848
Fluvastatin SodiumCapsule20 mg/1OralCarilion Materials Management2013-03-19Not applicableUs00378 8020 77 nlmimage10 043b0248
Fluvastatin SodiumTablet, film coated, extended release80 mg/1OralMylan Pharmaceuticals Inc.2015-09-11Not applicableUs0378 512120180907 15195 1hb6qrp
Fluvastatin SodiumTablet, film coated, extended release80 mg/1OralTeva Pharmaceuticals USA, Inc.2016-06-02Not applicableUs
Fluvastatin SodiumCapsule40 mg/1OralCarilion Materials Management2013-03-19Not applicableUs68151 133420180907 15195 hvm7vh
Fluvastatin SodiumCapsule40 mg/1OralMylan Pharmaceuticals Inc.2013-03-19Not applicableUs00378 8021 93 nlmimage10 043b0218
Fluvastatin SodiumCapsule20 mg/1OralMylan Pharmaceuticals Inc.2013-03-19Not applicableUs0378 802020180913 8702 1hnkvpd
Fluvastatin Sodium ERTablet, extended release80 mg/1OralSandoz2015-10-16Not applicableUs
Fluvastatin Sodium ERTablet, extended release80 mg/1OralSandoz2015-10-16Not applicableUs
International/Other Brands
Canef (AstraZeneca) / Cranoc (Astellas)
Categories
UNII
4L066368AS
CAS number
93957-54-1
Weight
Average: 411.4659
Monoisotopic: 411.18458653
Chemical Formula
C24H26FNO4
InChI Key
FJLGEFLZQAZZCD-JUFISIKESA-N
InChI
InChI=1S/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m0/s1
IUPAC Name
(3S,5R,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
SMILES
CC(C)N1C(\C=C\[C@H](O)C[C@H](O)CC(O)=O)=C(C2=CC=C(F)C=C2)C2=CC=CC=C12

Pharmacology

Indication

To be used as an adjunct to dietary therapy to prevent cardiovascular events. May be used as secondary prevention in patients with coronary heart disease (CHD) to reduce the risk of requiring coronary revascularization procedures, for reducing progression of coronary atherosclerosis in hypercholesterolemic patients with CHD, and for the treatment of primary hypercholesterolemia and mixed dyslidipidemia.

Associated Conditions
Pharmacodynamics

Fluvastatin, the first synthetically-derived HMG-CoA reductase inhibitor, is a hydrophilic, acidic, antilipemic agent used to lower cholesterol and triglyceride levels associated with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb), to slow the progression of coronary atherosclerosis in patients with CHD and as secondary prevention therapy in patients with CHD to reduce the risk of requiring coronary revascularization procedures. Although similar to lovastatin, simvastatin, and pravastatin, fluvastatin has a shorter half-life, no active metabolites, extensive protein binding, and minimal CSF penetration. Fluvastatin acts primarily in the liver. It is prepared as a racemate of two erythro enantiomers of which the 3R,5S enantiomer exerts the pharmacologic effect.

Mechanism of action

Fluvastatin selectively and competitively inhibits the hepatic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate, the rate-limiting step in cholesterol biosynthesis. Inhibition results in a decrease in hepatic cholesterol levels which stimulates the synthesis of LDL receptors and increases hepatic uptake of LDL cholesterol. The end result is decreased levels of plasma total and LDL cholesterol.

TargetActionsOrganism
A3-hydroxy-3-methylglutaryl-coenzyme A reductase
inhibitor
Human
Absorption

Rapidly and almost completely absorbed (> 90%), but undergoes extensive first pass metabolism. Bioavailability is 24% (range 9-50%) when a 10 mg dose is given. The mean relative bioavailability of the extended-release tablet is 29% (range: 9% to 66%) compared to an immediate-release capsule administered under fasting conditions. When given orally, fluvastatin reaches peak concentrations (Tmax) in less than one hour. Taking the extended release tablet with a high-fat meal will delay absorption (Tmax = 6 hours) and increase bioavailability by approximately 50%. However, the maximum concentration of fluvastatin sodium extended-release tablets seen after a high fat meal is less than the peak concentration following a single dose or twice daily dose of the 40 mg fluvastatin capsule.

Volume of distribution
  • 0.35 L/kg
Protein binding

98% bound to plasma proteins. At therapeutic concentrations, the protein binding of fluvastatin is not affected by warfarin, salicylic acid and glyburide.

Metabolism

Undergoes hepatic metabolism primarily via hydroxylation of the indole ring at the 5- and 6-positions to 5-hydroxy fluvastatin and 6-hydroxy fluvastatin, respectively. N-dealkylation to N-desisopropyl fluvastatin and beta-oxidation of the side chain also occurs. Metabolized primarily by the CYP2C9 isozyme system (75%), and to a lesser extent by CYP3A4 (~20%) and CYP2C8 (~5%). Hydroxylated metabolites retain some pharmcological activity, but are present as conjugates (glucuronides and sulfates) in the blood and are rapidly eliminated via bile into feces. Both enantiomers of fluvastatin are metabolized in a similar manner. Fluvastatin also undergoes glucuronidation via UGT enzymes.

Route of elimination

When orally administered, fluvastatin is primarily excreted in the faces ( ~90%) as metabolites, with less than 2% present as unchanged drug. Approximately 5% was recovered in the urine.

Half life

3 hours

Clearance
  • 0.8 L/h/kg
  • 107 ± 38.1 L/h [Hypercholesterolemia patients receiving a single dose of 20 mg]
  • 87.8 ± 45 L/h [Hypercholesterolemia patients receiving 20 mg twice daily]
  • 108 ± 44.7 L/h [Hypercholesterolemia patients receiving 40 mg single]
  • 64.2 ± 21.1 L/h [Hypercholesterolemia patients receiving 40 mg twice daily]
Toxicity

Generally well-tolerated. May cause gastrointestinal upset (diarrhea, nausea, constipation, gas, abdominal pain), myotoxicity (mypothy, myositis, rhabdomyolysis), and hepatotoxicity.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Fluvastatin Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Fluvastatin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Fluvastatin.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Fluvastatin.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Fluvastatin.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Fluvastatin.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Fluvastatin.
6-Deoxyerythronolide BThe metabolism of Fluvastatin can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Fluvastatin.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Fluvastatin.
AbirateroneThe metabolism of Fluvastatin can be decreased when combined with Abiraterone.
Food Interactions
  • May be taken with or without food, but should be taken consistently.
  • When given with an evening meal, Cmax and AUC decreased while Tmax increased 2-fold

References

Synthesis Reference

Gustavo Frenkel, Eyal Gilboa, "Process for the preparation of fluvastatin sodium crystal form XIV." U.S. Patent US20050119342, issued June 02, 2005.

US20050119342
General References
  1. Toda T, Eliasson E, Ask B, Inotsume N, Rane A: Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):327-32. doi: 10.1111/j.1742-7843.2009.00453.x. Epub 2009 Aug 6. [PubMed:19663817]
External Links
Human Metabolome Database
HMDB0015227
KEGG Drug
D07983
KEGG Compound
C07014
PubChem Compound
1548972
PubChem Substance
46505668
ChemSpider
1265982
ChEBI
5136
ChEMBL
CHEMBL350239
Therapeutic Targets Database
DAP000554
PharmGKB
PA449688
HET
115
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Fluvastatin
ATC Codes
C10AA04 — Fluvastatin
AHFS Codes
  • 24:06.08 — Hmg-coa Reductase Inhibitors
FDA label
Download (84.5 KB)
MSDS
Download (101 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1RecruitingTreatmentGliomas1
2CompletedBasic ScienceAntiphospholipid Syndrome1
2CompletedTreatmentAlport Syndrome1
2CompletedTreatmentCancer, Breast1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentProstate Cancer1
2TerminatedPreventionAging / Inflammatory Reaction1
2Unknown StatusTreatmentAortic Valve Stenosis1
2WithdrawnTreatmentHepatitis C Viral Infection / Hepatitis C Virus (HCV) Infection1
2, 3TerminatedPreventionTransplantation, Renal1
3CompletedTreatmentAtherosclerosis / Cardiovascular Disease (CVD)1
3CompletedTreatmentChronic Nephropathy / High Blood Pressure (Hypertension) / Proteinuria1
3CompletedTreatmentDyslipidemias1
3CompletedTreatmentHeterozygous Familial Hypercholesterolemia / Mixed hypercholesterolemia1
3CompletedTreatmentHigh Cholesterol1
3CompletedTreatmentHigh Cholesterol / Mixed hypercholesterolemia1
3RecruitingTreatmentHigh Cholesterol2
3TerminatedTreatmentHigh Cholesterol1
4CompletedNot AvailableDrug-Interactions1
4CompletedPreventionGraft Vasculopathy1
4CompletedTreatmentChronic Stable Angina Pectoris / Non ST Segment Elevation Myocardial Infarction (NSTEMI) / Unstable Angina Pectoris1
4CompletedTreatmentCoronary Heart Disease (CHD) / High Cholesterol1
4CompletedTreatmentCoronary Heart Disease (CHD) / Myocardial Infarction1
4CompletedTreatmentDyslipidemias3
4CompletedTreatmentDyslipidemias / High Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Cholesterol1
4CompletedTreatmentHypertension, Dyslypidaemia1
4CompletedTreatmentLipid Metabolism Disorders1
4CompletedTreatmentMetabolic Syndromes2
4CompletedTreatmentOsteoporosis1
4RecruitingBasic ScienceAdipose Tissue, Brown / Clinical Trial / Insulin Resistance1
4RecruitingPreventionHigh Blood Pressure (Hypertension) / Strokes / Transient Ischaemic Attack (TIA)1
4RecruitingTreatmentCoronary Artery Disease1
4SuspendedPreventionAortic Valve Stenosis1
4Unknown StatusPreventionHeart Transplantation / High Cholesterol1
4Unknown StatusTreatmentAtherosclerosis / Coronary Heart Disease (CHD)1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableHigh Cholesterol1
Not AvailableCompletedPreventionAtherosclerosis1
Not AvailableCompletedTreatmentHepatitis C Viral Infection1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Direct Dispensing Inc.
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
Tablet, film coated, extended releaseOral80 mg/1
CapsuleOral20 mg/1
CapsuleOral40 mg/1
CapsuleOral20 mg
CapsuleOral40 mg
Tablet, extended releaseOral80 mg/1
Tablet, extended releaseOral80 mg
Prices
Unit descriptionCostUnit
Lescol XL 80 mg 24 Hour tablet4.25USD tablet
Lescol xl 80 mg tablet4.24USD tablet
Lescol xl 80 mg tablet sa3.66USD tablet
Lescol 20 mg capsule3.38USD capsule
Lescol 40 mg capsule3.37USD capsule
Lescol Xl 80 mg Extended-Release Tablet1.62USD tablet
Lescol 40 mg Capsule1.35USD capsule
Lescol 20 mg Capsule0.96USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5354772No1994-10-112011-10-11Us
CA2346868No2008-09-092019-10-12Canada
CA2085037No2000-11-282012-12-10Canada
US6242003Yes2001-06-052020-10-13Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)194-197 °CHojjati, Mohammad; Journal of Supercritical Fluids 2007, V41(2), P187-194 CAPLUS
water solubility0.46 mg/LNot Available
logP4.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00441 mg/mLALOGPS
logP3.69ALOGPS
logP3.83ChemAxon
logS-5ALOGPS
pKa (Strongest Acidic)4.56ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area82.69 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity114.86 m3·mol-1ChemAxon
Polarizability44.31 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9943
Blood Brain Barrier+0.9382
Caco-2 permeable-0.5053
P-glycoprotein substrateNon-substrate0.5176
P-glycoprotein inhibitor INon-inhibitor0.7395
P-glycoprotein inhibitor IINon-inhibitor0.8381
Renal organic cation transporterNon-inhibitor0.8823
CYP450 2C9 substrateNon-substrate0.7305
CYP450 2D6 substrateSubstrate0.8918
CYP450 3A4 substrateSubstrate0.6111
CYP450 1A2 substrateNon-inhibitor0.6003
CYP450 2C9 inhibitorNon-inhibitor0.675
CYP450 2D6 inhibitorNon-inhibitor0.8983
CYP450 2C19 inhibitorNon-inhibitor0.6314
CYP450 3A4 inhibitorNon-inhibitor0.8811
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.809
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.7909
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.9472 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9899
hERG inhibition (predictor II)Non-inhibitor0.848
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpyrroles. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrrole ring through a CC or CN bond.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyrroles
Sub Class
Substituted pyrroles
Direct Parent
Phenylpyrroles
Alternative Parents
N-alkylindoles / Indoles / Medium-chain hydroxy acids and derivatives / Medium-chain fatty acids / Beta hydroxy acids and derivatives / Fluorobenzenes / Halogenated fatty acids / Heterocyclic fatty acids / Hydroxy fatty acids / Unsaturated fatty acids
show 12 more
Substituents
3-phenylpyrrole / N-alkylindole / Indole / Indole or derivatives / Medium-chain hydroxy acid / Medium-chain fatty acid / Beta-hydroxy acid / Fluorobenzene / Halobenzene / Halogenated fatty acid
show 28 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
statin (synthetic), (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid (CHEBI:5136)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Nadph binding
Specific Function
Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including...
Gene Name
HMGCR
Uniprot ID
P04035
Uniprot Name
3-hydroxy-3-methylglutaryl-coenzyme A reductase
Molecular Weight
97475.155 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. 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. doi: 10.1517/14728210802676278 . [PubMed:19249983]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
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:19515014]
  2. Kocarek TA, Reddy AB: Regulation of cytochrome P450 expression by inhibitors of hydroxymethylglutaryl-coenzyme A reductase in primary cultured rat hepatocytes and in rat liver. Drug Metab Dispos. 1996 Nov;24(11):1197-204. [PubMed:8937853]
  3. Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP, Robinson WT: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos. 1999 Mar;27(3):410-6. [PubMed:10064574]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP, Robinson WT: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos. 1999 Mar;27(3):410-6. [PubMed:10064574]
  2. Toda T, Eliasson E, Ask B, Inotsume N, Rane A: Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):327-32. doi: 10.1111/j.1742-7843.2009.00453.x. Epub 2009 Aug 6. [PubMed:19663817]
  3. Scripture CD, Pieper JA: Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001;40(4):263-81. [PubMed:11368292]
  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:19515014]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Kivisto KT, Niemi M, Schaeffeler E, Pitkala K, Tilvis R, Fromm MF, Schwab M, Eichelbaum M, Strandberg T: Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics. 2004 Aug;14(8):523-5. [PubMed:15284534]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP, Robinson WT: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos. 1999 Mar;27(3):410-6. [PubMed:10064574]
  2. Toda T, Eliasson E, Ask B, Inotsume N, Rane A: Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):327-32. doi: 10.1111/j.1742-7843.2009.00453.x. Epub 2009 Aug 6. [PubMed:19663817]
  3. Scripture CD, Pieper JA: Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001;40(4):263-81. [PubMed:11368292]
  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:19515014]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  6. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Fischer V, Johanson L, Heitz F, Tullman R, Graham E, Baldeck JP, Robinson WT: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos. 1999 Mar;27(3):410-6. [PubMed:10064574]
  2. Toda T, Eliasson E, Ask B, Inotsume N, Rane A: Roles of different CYP enzymes in the formation of specific fluvastatin metabolites by human liver microsomes. Basic Clin Pharmacol Toxicol. 2009 Nov;105(5):327-32. doi: 10.1111/j.1742-7843.2009.00453.x. Epub 2009 Aug 6. [PubMed:19663817]
  3. Scripture CD, Pieper JA: Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001;40(4):263-81. [PubMed:11368292]
  4. Meadowcroft AM, Williamson KM, Patterson JH, Hinderliter AL, Pieper JA: The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers. J Clin Pharmacol. 1999 Apr;39(4):418-24. [PubMed:10197301]
  5. Wu JC, Nafziger AN, Bertino JS Jr, Ma JD: Limitations of S-warfarin truncated area under the concentration-time curve to predict cytochrome P450 2c9 activity. Drug Metab Lett. 2012 Jun 1;6(2):94-101. [PubMed:22594566]
  6. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  7. Fluvastatin FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
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:11523064]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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:11523064]
  2. Scripture CD, Pieper JA: Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001;40(4):263-81. [PubMed:11368292]
  3. 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:19515014]
  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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. 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:12433810]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Kopplow K, Letschert K, Konig J, Walter B, Keppler D: Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol. 2005 Oct;68(4):1031-8. Epub 2005 Jul 26. [PubMed:16046661]
  2. Karlgren M, Ahlin G, Bergstrom CA, Svensson R, Palm J, Artursson P: In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions. Pharm Res. 2012 Feb;29(2):411-26. doi: 10.1007/s11095-011-0564-9. Epub 2011 Aug 23. [PubMed:21861202]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Kopplow K, Letschert K, Konig J, Walter B, Keppler D: Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol. 2005 Oct;68(4):1031-8. Epub 2005 Jul 26. [PubMed:16046661]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Kopplow K, Letschert K, Konig J, Walter B, Keppler D: Human hepatobiliary transport of organic anions analyzed by quadruple-transfected cells. Mol Pharmacol. 2005 Oct;68(4):1031-8. Epub 2005 Jul 26. [PubMed:16046661]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Ekins S, Johnston JS, Bahadduri P, D'Souza VM, Ray A, Chang C, Swaan PW: In vitro and pharmacophore-based discovery of novel hPEPT1 inhibitors. Pharm Res. 2005 Apr;22(4):512-7. Epub 2005 Apr 7. [PubMed:15846457]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
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:23562342]

Drug created on June 13, 2005 07:24 / Updated on November 20, 2018 13:19