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Identification
Name Ibuprofen
Accession Number DB01050 (APRD00372)
Type small molecule
Groups approved
Description

Ibuprofen, a propionic acid derivative, is a prototypical nonsteroidal anti-inflammatory agent (NSAIA) with analgesic and antipyretic properties.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Ibuprophen
  • P-Isobutylhydratropic Acid
  • Para-Isobutylhydratropic Acid
Brand names
  • Actiprofen
  • Adran
  • Advil
  • Advil Liqui-Gels
  • Amersol
  • Amibufen
  • Anco
  • Andran
  • Anflagen
  • Apo-Ibuprofen
  • Apsifen
  • Apsifen-F
  • Artril 300
  • Bluton
  • Brufanic
  • Brufen
  • Brufort
  • Buburone
  • Butylenin
  • Cap-Profen
  • Children's Advil
  • Children's Elixsure
  • Children's Ibuprofen
  • Children's Motrin
  • Codral
  • Dolgin
  • Dolgirid
  • Dolgit
  • Dolo-Dolgit
  • Dolocyl
  • Ebufac
  • Epobron
  • Femadon
  • Fenbid Spansule
  • Haltran
  • Ibu
  • Ibu-Attritin
  • Ibu-Slo
  • Ibu-Tab
  • Ibu-Tab 200
  • Ibufen
  • Ibumetin
  • Ibuprin
  • Ibuprocin
  • Ibuprohm
  • Ibutid
  • Ifen
  • Inabrin
  • Inoven
  • Junior Strength Advil
  • Junior Strength Ibuprofen
  • Junior Strength Motrin
  • Lamidon
  • Lebrufen
  • Lidifen
  • Liptan
  • Medipren
  • Midol
  • Midol 200
  • Motrin
  • Mynosedin
  • Napacetin
  • NeoProfen (Ovation)
  • Nobfelon
  • Nobfen
  • Nobgen
  • Novogent N
  • Novoprofen
  • Nuprin
  • Nurofen
  • Pantrop
  • Paxofen
  • Pedia-Profen
  • Pediaprofen
  • Pediatric Advil
  • Profen
  • Rafen
  • Rebugen
  • Roidenin
  • Rufen
  • Seclodin
  • Suspren
  • Tab-Profen
  • Tabalon
  • Trendar
  • Urem
Brand name mixtures
  • Advil® Cold & Sinus (ibuprofen + pseudoephedrine HCl)
  • Advil® Cold & Sinus Daytime (ibuprofen + pseudoephedrine HCl)
  • Advil® Cold and Sinus Nighttime (ibuprofen + pseudoephedrine HCll + chlorpheniramine maleate)
  • Advil® Cold and Sinus Plus (ibuprofen + pseudoephedrine HCl + chlorpheniramine maleate)
  • Advil® Flu & Body Ache (ibuprofen + pseudoephedrine HCl)
  • Children's Advil® Cold (ibuprofen + pseudoephedrine HCl)
  • Dristan® Sinus Caplets® (ibuprofen + pseudoephedrine HCl)
  • Motrin® Children's Cold (ibuprofen + pseudoephedrine HCl)
  • Motrin® Sinus Headache (ibuprofen + pseudoephedrine HCl)
  • Robax Platinum® (methocarbamol + ibuprofen)
  • Sudafed® Sinus Advance (ibuprofen + pseudoephedrine HCl)
  • Vicoprofen® (ibuprofen + hydrocodone bitartrate)
Categories
  • Anti-inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Analgesics
  • Analgesics, Non-Narcotic
  • Antipyretics
  • Nonsteroidal Anti-inflammatory Agents (NSAIAs)
CAS number 15687-27-1
Weight Average: 206.2808
Monoisotopic: 206.130679820
Chemical Formula C13H18O2
InChI Key InChIKey=HEFNNWSXXWATRW-UHFFFAOYSA-N
InChI
InChI=1S/C13H18O2/c1-9(2)8-11-4-6-12(7-5-11)10(3)13(14)15/h4-7,9-10H,8H2,1-3H3,(H,14,15)
Plain Text
IUPAC Name
2-[4-(2-methylpropyl)phenyl]propanoic acid
SMILES
CC(C)CC1=CC=C(C=C1)C(C)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Phenylacetates
Substructures
  • Hydroxy Compounds
  • Acetates
  • Carboxylic Acids and Derivatives
  • Phenylacetates
  • Benzene and Derivatives
  • Aromatic compounds
Pharmacology
Indication For symptomatic treatment of rheumatoid arthritis, juvenile rheumatoid arthritis and osteoarthritis. May be used to treat mild to moderate pain and for the management of dysmenorrhea. May be used to reduce fever. Has been used with some success for treating ankylosing spondylitis, gout and psoriatic arthritis. May reduce pain, fever and inflammation of pericarditis. May be used IV with opiates to relieve moderate to severe pain. Ibuprofen lysine may be used IV to treat patent ductus arteriosus (PDA) in premature neonates.
Pharmacodynamics Ibuprofen is a nonsteroidal anti-inflammatory agent (NSAIA) or nonsteroidal anti-inflammatory drug (NSAID), with analgesic and antipyretic properties. Ibuprofen has pharmacologic actions similar to those of other prototypical NSAIAs, which are thought to act through inhibition of prostaglandin synthesis.
Mechanism of action The exact mechanism of action of ibuprofen is unknown. Ibuprofen is a non-selective inhibitor of cyclooxygenase, an enzyme invovled in prostaglandin synthesis via the arachidonic acid pathway. Its pharmacological effects are believed to be due to inhibition cylooxygenase-2 (COX-2) which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling. Antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation. Inhibition of COX-1 is thought to cause some of the side effects of ibuprofen including GI ulceration. Ibuprofen is administered as a racemic mixture. The R-enantiomer undergoes extensive interconversion to the S-enantiomer in vivo. The S-enantiomer is believed to be the more pharmacologically active enantiomer.
Absorption ~ 80% absorbed from GI tract

Time to reach peak plasma concentration = 47 minutes (suspension), 62 minutes (chewable tablets), 120 minutes (conventional tablets)
Volume of distribution Not Available
Protein binding 90-99% to whole human plasma and site II of purified albumin, binding appears to be saturable and becomes non-linear at concentrations exceeding 20 mcg/ml.
Metabolism

R-enanatiomer undergoes extensive enantiomeric conversion (53-65%) to the more active S-enantiomer in vivo. Metablized by oxidation to 2 inactive metabolites: (+)-2[4´-(2-hydroxy-2-methylpropyl)phenyl]propionic acid and (+)-2-[4´-(2-carboxypropyl)phenyl]propionic acid. Very small amounts of 1-hydroxyibuprofen and 3-hydroxyibuprofen have been recovered from urine. Cytochrome P450 2C9 is the major catalyst in the formation of oxidative metabolites. Oxidative metabolites may be conjugated to glucuronide prior to excretion.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 2C9 2-Hydroxyibuprofen 2-hydroxylation
Cytochrome P450 2C9 3-Hydroxyibuprofen 3-hydroxylation 53 0.58
Cytochrome P450 2C8 2-Hydroxyibuprofen 2-hydroxylation
Cytochrome P450 2C8 3-Hydroxyibuprofen 3-hydroxylation
UDP-glucuronosyltransferase 1-9 Ibuprofen glucuronide glucuronidation
UDP-glucuronosyltransferase 1-1 Ibuprofen glucuronide glucuronidation
UDP-glucuronosyltransferase 1-3 Ibuprofen glucuronide glucuronidation
UDP-glucuronosyltransferase 2B7 Ibuprofen glucuronide glucuronidation
UDP-glucuronosyltransferase 2B4 Ibuprofen glucuronide glucuronidation
Route of elimination Ibuprofen is rapidly metabolized and eliminated in the urine.
Half life 2-4 hours
Clearance Not Available
Toxicity

Side effects: May cause peripheral edema and fluid retention. Use caution in patients with congestive heart failure or severe uncontrolled hypertension. May cause dyspepsia, heartburn, nausea, vomiting, anorexia, diarrhea, constipation, stomatitis, flatulence, bloating, epigastric pain, and abdominal pain. Peptic ulcer and GI bleeding have been reported. May also cause dizziness, headache and nervousness. Acute renal failure accompanied by acute tubular necrosis has been reported.

Most common symptoms of overdose are abdominal pain, nausea, vomiting, lethargy, vertigo, drowsiness (somnolence), dizziness and insomnia. Other symptoms of overdose include headache, loss of consciousness, tinnitus, CNS depression, convulsions and seizures. May rarely cause metabolic acidosis, abnormal hepatic function, hyperkalemia, renal failure, dyspnea, respiratory depression, coma, acute renal failure, and apnea (primarily in very young pediatric patients).

LD50=1255mg/kg(orally in mice)
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00086 Ibuprofen Pathway SMP00086
Pharmacoeconomics
Manufacturers
  • Wyeth consumer healthcare
  • Banner pharmacaps inc
  • Contract pharmacal corp
  • Dr reddys laboratories ltd
  • Marksans pharma ltd
  • Bayer healthcare llc
  • Cumberland pharmaceuticals inc
  • Mcneil consumer healthcare
  • Perrigo co
  • Tris pharma inc
  • Mcneil consumer products co div mcneilab inc
  • Alterna tchp llc
  • L perrigo co
  • Abbott laboratories pharmaceutical products div
  • Actavis mid atlantic llc
  • Perrigo r and d co
  • Mcneil consumer healthcare div mcneil ppc inc
  • Mcneil pediatrics
  • Lederle laboratories div american cyanamid co
  • Basf corp
  • Pliva inc
  • Advent pharmaceuticals inc
  • Amneal pharmaceuticals ny llc
  • Dr reddys laboratories louisiana llc
  • Dr reddys laboratories inc
  • Halsey drug co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Leiner health products inc
  • Lnk international inc
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Mylan laboratories inc
  • Northstar healthcare holdings ltd
  • Ohm corp
  • Ohm laboratories inc
  • Par pharmaceutical inc
  • Purepac pharmaceutical co
  • Sandoz inc
  • Shasun usa inc
  • Superpharm corp
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals inc
  • Watson laboratories inc
  • Alra laboratories inc
  • Bristol myers products inc
  • Lundbeck inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral 200 mg
Concentrate Intravenous 100 mg/ml
Suspension Oral 100 mg/5 ml
Suspension Oral 40 mg/ml
Tablet Oral 200 mg
Tablet Oral 400 mg
Tablet Oral 600 mg
Tablet Oral 800 mg
Tablet, chewable Oral 100 mg
Tablet, chewable Oral 50 mg
Tablet, film coated Oral 100 mg
Tablet, film coated Oral 200 mg
Tablet, film coated Oral 400 mg
Tablet, film coated Oral 600 mg
Tablet, film coated Oral 800 mg
Prices
Unit description Cost Unit
Neoprofen 20 mg/2 ml vial 304.5 USD ml
Caldolor 400 mg/4 ml vial 2.21 USD ml
Caldolor 800 mg/8 ml vial 1.58 USD ml
Nuprin arthritis patch 1.11 USD patch
Ibuprofen powder 1.04 USD g
Nuprin muscle & joint patch 1.03 USD patch
Profen II 45-800 mg 12 Hour tablet 0.69 USD tablet
Motrin 800 mg tablet 0.59 USD tablet
Advil allergy sinus caplet 0.5 USD caplet
Ibu-drops 40 mg/ml suspension drops 0.42 USD ml
Motrin 600 mg tablet 0.4 USD tablet
Ibuprofen 800 mg tablet 0.36 USD tablet
Ibuprofen 400 mg tablet 0.35 USD tablet
Infant's motrin 50 mg/1.25 ml 0.34 USD ml
Childs ibuprofen susp drp 0.33 USD ml
Ibuprofen 600 mg tablet 0.33 USD tablet
Wal-profen cold & sinus cplt 0.3 USD caplet
Infant ibuprofen susp drop 0.29 USD ml
Motrin 400 mg tablet 0.29 USD tablet
CVS Pharmacy infant ibuprofen susp drop 0.25 USD ml
Infants medi-profen susp 0.23 USD ml
Advil cold & sinus caplet 0.22 USD caplet
Advil pm caplet 0.22 USD caplet
Soba profen cold-sinus tablet 0.22 USD tablet
Midol caplet 0.21 USD caplet
Advil migraine 200 mg capsule 0.2 USD capsule
Ibuprofen cold-sinus caplet 0.2 USD caplet
Motrin 100 mg caplet 0.2 USD caplet
Motrin pm caplet 0.2 USD caplet
Advil 200 mg liqui-gel capsule 0.19 USD capsule
Soba profen ib caplet 0.19 USD caplet
Motrin 100 mg tablet chew 0.18 USD tablet
Pub infants profenib drops 0.18 USD ml
Sm ibuprofen ib 100 mg tablet 0.18 USD tablet
Eck ibuprofen jr caplet 0.17 USD caplet
Ibuprofen pm caplet 0.17 USD caplet
Advil 200 mg caplet 0.15 USD capsule
Advil 200 mg gel caplet 0.15 USD caplet
Advil 200 mg tablet 0.15 USD tablet
Ibuprofen 100 mg tablet chew 0.15 USD tablet
Motrin ib 200 mg caplet 0.15 USD caplet
Apo-Ibuprofen 600 mg Tablet 0.14 USD tablet
CVS Pharmacy ibuprofen jr str 100 mg tablet 0.14 USD tablet
Nu-Ibuprofen 600 mg Tablet 0.14 USD tablet
Motrin ib 200 mg tablet 0.13 USD tablet
Motrin ib 200 mg gelcap 0.12 USD capsule
Nuprin 200 mg caplet 0.12 USD caplet
Wal-profen 200 mg caplet 0.12 USD caplet
Wal-profen 200 mg tablet 0.12 USD tablet
Eql ibuprofen 200 mg tablet 0.1 USD tablet
Nuprin 200 mg tablet 0.1 USD tablet
Apo-Ibuprofen 400 mg Tablet 0.08 USD tablet
Ibuprofen ib 200 mg tablet 0.08 USD tablet
Novo-Profen 400 mg Tablet 0.08 USD tablet
Apo-Ibuprofen 300 mg Tablet 0.07 USD tablet
Medi-profen 200 mg tablet 0.07 USD tablet
Ibuprofen 100 mg/5ml Suspension 0.06 USD ml
Ibuprofen 200 mg caplet 0.06 USD caplet
Child ibuprofen susp 0.05 USD ml
Children's medi-profen susp 0.05 USD ml
Children's motrin cold suspension 0.05 USD ml
CVS Pharmacy ibuprofen 200 mg tablet 0.05 USD tablet
Ibuprofen cold suspension 0.05 USD ml
I-prin 200 mg tablet 0.05 USD tablet
Novo-Profen 600 mg Tablet 0.05 USD tablet
Children's motrin cold 0.04 USD ml
Pv ibuprofen 200 mg caplet 0.04 USD caplet
Soba children's profenib susp 0.04 USD ml
Ibuprofen 200 mg tablet 0.03 USD tablet
CVS Pharmacy ibuprofen 200 mg caplet 0.02 USD caplet
Pv ibuprofen 200 mg tablet 0.02 USD tablet
Patents
Country Patent Number Approved Expires
United States 6727286 2001-11-27 2021-11-27
United States 5215755 1993-06-01 2010-06-01
Properties
State solid
Melting point 75 - 77 oC
Experimental Properties
Property Value Source
water solubility 0.049 mg/ml PhysProp
logP 3.6 PhysProp
logS -3.99 [ADME Research, USCD] PhysProp
Caco2 permeability -4.28 [ADME Research, USCD] BiGG
pKa 4.91 Various sources
Predicted Properties
Property Value Source
water solubility 6.84e-02 g/l ALOGPS
logP 3.50 ALOGPS
logP 3.84 ChemAxon Molconvert
logS -3.48 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 1 ChemAxon Molconvert
polar surface area 37.30 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 60.73 ChemAxon Molconvert
polarizability 23.76 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Zawada ET Jr: Renal consequences of nonsteroidal antiinflammatory drugs. Postgrad Med. 1982 May;71(5):223-30. Pubmed
  2. Townsend KP, Pratico D: Novel therapeutic opportunities for Alzheimer’s disease: focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005 Oct;19(12):1592-601. Pubmed
  3. Chen H, Jacobs E, Schwarzschild MA, McCullough ML, Calle EE, Thun MJ, Ascherio A: Nonsteroidal antiinflammatory drug use and the risk for Parkinson’s disease. Ann Neurol. 2005 Dec;58(6):963-7. Pubmed
  4. Geisslinger G, Dietzel K, Bezler H, Nuernberg B, Brune K: Therapeutically relevant differences in the pharmacokinetical and pharmaceutical behavior of ibuprofen lysinate as compared to ibuprofen acid. Int J Clin Pharmacol Ther Toxicol. 1989 Jul;27(7):324-8. Pubmed
  5. Bergner T, Przybilla B: Photosensitization caused by ibuprofen. J Am Acad Dermatol. 1992 Jan;26(1):114-6. Pubmed
External Links
Resource Link
KEGG Drug D00126 Link_out
KEGG Compound C01588 Link_out
PubChem Compound 3672 Link_out
PubChem Substance 46507255 Link_out
ChemSpider 3544 Link_out
ChEBI 5855 Link_out
ChEMBL 5855 Link_out
Therapeutic Targets Database DAP000780 Link_out
PharmGKB PA449957 Link_out
HET IBP Link_out
Drug Product Database 636525 Link_out
RxList http://www.rxlist.com/cgi/generic/ibup.htm Link_out
Drugs.com http://www.drugs.com/ibuprofen.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Ibuprofen Link_out
ATC Codes
  • C01EB16
  • G02CC01
  • M01AE01
  • M01AE14
  • M02AA13
AHFS Codes
  • 28:08.04.92
PDB Entries Not Available
FDA label show (1.8 MB)
MSDS show (73.5 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol.
  • Food delays the time to reach peak plasma concentrations by 30-60 minutes and reduces peak plasma concentrations by 30-50%. Extent of absorption is unaffected.
  • Take with food to reduce gastric irritation.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: yes
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. Pubmed
  2. Ouellet M, Falgueyret JP, Percival MD: Detergents profoundly affect inhibitor potencies against both cyclo-oxygenase isoforms. Biochem J. 2004 Feb 1;377(Pt 3):675-84. Pubmed
  3. Gallego-Sandin S, Novalbos J, Rosado A, Gisbert JP, Galvez-Mugica MA, Garcia AG, Pajares JM, Abad-Santos F: Effect of ibuprofen on cyclooxygenase and nitric oxide synthase of gastric mucosa: correlation with endoscopic lesions and adverse reactions. Dig Dis Sci. 2004 Sep;49(9):1538-44. Pubmed
  4. Murphey LJ, Williams MK, Sanchez SC, Byrne LM, Csiki I, Oates JA, Johnson DH, Morrow JD: Quantification of the major urinary metabolite of PGE2 by a liquid chromatographic/mass spectrometric assay: determination of cyclooxygenase-specific PGE2 synthesis in healthy humans and those with lung cancer. Anal Biochem. 2004 Nov 15;334(2):266-75. Pubmed
  5. Sanchez-Fidalgo S, Martin-Lacave I, Illanes M, Motilva V: Angiogenesis, cell proliferation and apoptosis in gastric ulcer healing. Effect of a selective cox-2 inhibitor. Eur J Pharmacol. 2004 Nov 28;505(1-3):187-94. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Prostaglandin G/H synthase 1

Pharmacological action: yes

May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells

Organism class: human
UniProt ID: P23219 Link_out
Gene: PTGS1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51. Pubmed
  2. Patrignani P: Aspirin insensitive eicosanoid biosynthesis in cardiovascular disease. Thromb Res. 2003 Jun 15;110(5-6):281-6. Pubmed
  3. Gupta K, Kaub CJ, Carey KN, Casillas EG, Selinsky BS, Loll PJ: Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors. Bioorg Med Chem Lett. 2004 Feb 9;14(3):667-71. Pubmed
  4. Martic M, Tatic I, Markovic S, Kujundzic N, Kostrun S: Synthesis, biological activity and molecular modeling studies of novel COX-1 inhibitors. Eur J Med Chem. 2004 Feb;39(2):141-51. Pubmed
  5. Hillarp A: [Acetylsalicylic acid resistance—clinical diagnosis with unclear mechanism] Lakartidningen. 2004 Nov 4;101(45):3504-6, 3508-9. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 2C9

Actions: substrate, inhibitor

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

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

References:
  1. Mo SL, Zhou ZW, Yang LP, Wei MQ, Zhou SF: New insights into the structural features and functional relevance of human cytochrome P450 2C9. Part I. Curr Drug Metab. 2009 Dec;10(10):1075-126. Pubmed
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
  3. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  4. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
  5. Carlile DJ, Hakooz N, Bayliss MK, Houston JB: Microsomal prediction of in vivo clearance of CYP2C9 substrates in humans. Br J Clin Pharmacol. 1999 Jun;47(6):625-35. Pubmed

2. Cytochrome P450 2C8

Actions: substrate

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

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

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

3. Cytochrome P450 2C19

Actions: substrate

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

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

References:
  1. 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. UDP-glucuronosyltransferase 1-1

Actions: substrate

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 IX-alpha-C8 and IX-alpha-C12 monoconjugates and diconjugate

UniProt ID: P22309 Link_out
Gene: UGT1A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

5. UDP-glucuronosyltransferase 1-3

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds

UniProt ID: P35503 Link_out
Gene: UGT1A3 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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

6. UDP-glucuronosyltransferase 1-9

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols

UniProt ID: O60656 Link_out
Gene: UGT1A9 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

7. UDP-glucuronosyltransferase 2B4

Actions: substrate

UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme is active on polyhydroxylated estrogens (such as estriol, 4-hydroxyestrone and 2-hydroxyestriol) and xenobiotics (such as 4-methylumbelliferone, 1-naphthol, 4- nitrophenol, 2-aminophenol, 4-hydroxybiphenyl and menthol). It is capable of 6 alpha-hydroxyglucuronidation of hyodeoxycholic acid

UniProt ID: P06133 Link_out
Gene: UGT2B4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

8. UDP-glucuronosyltransferase 2B7

Actions: substrate

Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites

UniProt ID: P16662 Link_out
Gene: UGT2B7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

1. Solute carrier organic anion transporter family member 2B1

Actions: substrate

Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost

UniProt ID: O94956 Link_out
Gene: SLCO2B1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Satoh H, Yamashita F, Tsujimoto M, Murakami H, Koyabu N, Ohtani H, Sawada Y: Citrus juices inhibit the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos. 2005 Apr;33(4):518-23. Epub 2005 Jan 7. Pubmed

2. Multidrug resistance protein 1

Actions: substrate

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

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

References:
  1. Faassen F, Vogel G, Spanings H, Vromans H: Caco-2 permeability, P-glycoprotein transport ratios and brain penetration of heterocyclic drugs. Int J Pharm. 2003 Sep 16;263(1-2):113-22. Pubmed

3. Multidrug resistance-associated protein 4

Actions: inhibitor

May be an organic anion pump relevant to cellular detoxification

UniProt ID: O15439 Link_out
Gene: ABCC4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

4. Multidrug resistance-associated protein 1

Actions: inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M, Wijnholds J, Borst P: The human multidrug resistance protein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs. Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9244-9. Epub 2003 Jun 30. Pubmed

5. Solute carrier organic anion transporter family member 1A2

Actions: inhibitor

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

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

References:
  1. Shitara Y, Sugiyama D, Kusuhara H, Kato Y, Abe T, Meier PJ, Itoh T, Sugiyama Y: Comparative inhibitory effects of different compounds on rat oatpl (slc21a1)- and Oatp2 (Slc21a5)-mediated transport. Pharm Res. 2002 Feb;19(2):147-53. Pubmed

6. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mulato AS, Ho ES, Cihlar T: Nonsteroidal anti-inflammatory drugs efficiently reduce the transport and cytotoxicity of adefovir mediated by the human renal organic anion transporter 1. J Pharmacol Exp Ther. 2000 Oct;295(1):10-5. Pubmed
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  3. Uwai Y, Saito H, Inui K: Interaction between methotrexate and nonsteroidal anti-inflammatory drugs in organic anion transporter. Eur J Pharmacol. 2000 Dec 1;409(1):31-6. Pubmed
  4. Apiwattanakul N, Sekine T, Chairoungdua A, Kanai Y, Nakajima N, Sophasan S, Endou H: Transport properties of nonsteroidal anti-inflammatory drugs by organic anion transporter 1 expressed in Xenopus laevis oocytes. Mol Pharmacol. 1999 May;55(5):847-54. Pubmed

7. Solute carrier family 22 member 8

Actions: inhibitor

Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone- 3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed
  2. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  3. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. Pubmed

8. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamada M, Cha SH, Sekine T, Endou H: Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther. 2002 Aug;302(2):666-71. Pubmed
  2. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. Pubmed
Carriers

1. Serum albumin

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood

UniProt ID: P02768 Link_out
Gene: ALB Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Yamasaki K, Rahman MH, Tsutsumi Y, Maruyama T, Ahmed S, Kragh-Hansen U, Otagiri M: Circular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen. AAPS PharmSciTech. 2000 May 14;1(2):E12. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on January 20, 2011 08:18

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.