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Identification
Name Ibuprofen
Accession Number DB01050 (APRD00372)
Type small molecule
Groups Approved
Structure
Anti-inflammatory Agents
Cyclooxygenase Inhibitors
Analgesics
Categories
Analgesics, Non-Narcotic
Antipyretics
Hydroxy Compounds
Acetates
Aromatic compounds
Pharmacology
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
Indication
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.
Ibuprofen is a nonsteroidal anti-inflammatory agent (NSAIA) or nonsteroidal
anti-inflammatory drug (NSAID), with analgesic and antipyretic properties.
Pharmacodynamic
Ibuprofen has pharmacologic actions similar to those of other prototypical
s
NSAIAs, which are thought to act through inhibition of prostaglandin
synthesis.
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,
Mechanism of fever and swelling. Antipyretic effects may be due to action on the
action 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
Not Available
distribution
90-99% to whole human plasma and site II of purified albumin, binding
Protein binding appears to be saturable and becomes non-linear at concentrations exceeding
20 mcg/ml.
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.
UDP-
glucuronosyltransf
erase 1-1
Metabolism UDP-
glucuronosyltransf
erase 1-3
UDP-
Ibuprofen glucuronosyltransf Ibuprofen glucuronide Details
erase 1-9
UDP-
glucuronosyltransf
erase 2B4
UDP-
glucuronosyltransf
erase 2B7
Cytochrome P450
2C9
Cytochrome P450
2C8
Ibuprofen 3-Hydroxyibuprofen Details
Cytochrome P450
2C9
(+)-2-[4'-(2-
Ibuprofen carboxypropyl)phenyl]propioni Details
c acid
(+)-2[4'-(2-hydroxy-2-
Ibuprofen methylpropyl)phenyl]propionic Details
acid
Ibuprofen 1-hydroxyibuprofen Details
Ibuprofen Carboxy-ibuprofen Details
Route of
Ibuprofen is rapidly metabolized and eliminated in the urine.
elimination
Half life 2-4 hours
Clearance Not Available
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.
Toxicity 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
Humans and other mammals
organisms
Pathways
Ibuprofen Pathway SMP00086
Pharmacoeconomics
Manufacturers
Wyeth consumer healthcare
Perrigo co
L perrigo co
Perrigo r and d co
Mcneil pediatrics
Basf corp
Pliva inc
Ohm corp
Purepac pharmaceutical co
Sandoz inc
Superpharm corp
Lundbeck inc
Packagers
Abbott Laboratories Ltd.
Actavis Group
Amneal Pharmaceuticals
Apotheca Inc.
BASF Corp.
Bayer Healthcare
Blenheim Pharmacal
Breckenridge Pharmaceuticals
Bv Pharbita
Cardinal Health
Caremark LLC
Centrix Pharmaceuticals
Chain Drug
Corepharma LLC
Cumberland Pharmaceuticals
CVS Pharmacy
Dispensing Solutions
Dorx LLC
Eckerd
Equaline Vitamins
Gm Pharmaceuticals Inc.
Greenstone LLC
H and H Laboratories
Hawthorn Pharmaceuticals
Ivax Pharmaceuticals
LeaderPharma
Liberty Pharmaceuticals
Lundbeck Inc.
Major Pharmaceuticals
Mckesson Corp.
McNeil Laboratories
Medicine Shop
Medique Products
Medisca Inc.
Medvantx Inc.
Par Pharmaceuticals
PCA LLC
PD-Rx Pharmaceuticals Inc.
Perrigo Co.
Pharmaceutical Association
Pharmacia Inc.
Pharmedix
Prepackage Specialists
Prescript Pharmaceuticals
Qualitest
Redpharm Drug
Remedy Repack
Southwood Pharmaceuticals
Stat Rx Usa
Sunmark
UDL Laboratories
Va Cmop Dallas
Veratex Corp.
Vistapharm Inc.
Walgreen Co.
Watson Pharmaceuticals
Wyeth Pharmaceuticals
Xactdose Inc.
DrugBank does not sell nor buy drugs. Pricing information is supplied for
informational purposes only.
Country Patent Number Approved Expires (estimated)
Patents United States 6727286 2001-11-27 2021-11-27
United States 5215755 1993-06-01 2010-06-01
Properties
State Solid
Property Value Source
melting point 76 C PhysProp
YALKOWSKY,SH &
water solubility 21 mg/L (at 25 C)
DANNENFELSER,RM (1992)
Experimental
logP 3.97 AVDEEF,A (1997)
Properties
logS -3.99 ADME Research, USCD
Caco2
-4.28 ADME Research, USCD
permeability
pKa 4.91 SANGSTER (1994)
Predicted Property Value Source
Properties water solubility 6.84e-02 g/l ALOGPS
logP 3.5 ALOGPS
logP 3.84 ChemAxon
logS -3.5 ALOGPS
pKa (strongest acidic) 4.85 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor
2 ChemAxon
count
hydrogen donor count 1 ChemAxon
polar surface area 37.3 ChemAxon
rotatable bond count 4 ChemAxon
Refractivity 60.73 ChemAxon
Polarizability 23.76 ChemAxon
References
Synthesis
http://en.wikipedia.org/wiki/Ibuprofen#Synthesis
Reference
C01EB16
G02CC01
M01AE14
M02AA13
Avoid alcohol
Targets
May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in
activity-dependent plasticity
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
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
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002
Jan 1;30(1):412-5. Pubmed
May play an important role in regulating or promoting cell proliferation in some normal and
neoplastically transformed cells
References:
1. Chavez ML, DeKorte CJ: Valdecoxib: a review. Clin Ther. 2003 Mar;25(3):817-51.
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
6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002
Jan 1;30(1):412-5. Pubmed
References:
1. Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR,
Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal
anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012
Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. Pubmed
4. Thrombomodulin
Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex
with thrombin. This complex is responsible for the conversion of protein C to the activated
protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the
coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin
generated
1. Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR,
Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal
anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012
Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. Pubmed
Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single
Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an
important role in tissue remodeling and degradation, in cell migration and many other
physiopathological events. Play a direct role in facilitating neuronal migration
References:
1. Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR,
Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal
anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012
Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. Pubmed
FABP are thought to play a role in the intracellular transport of long-chain fatty acids and their
acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds
saturated long-chain fatty acids with a high affinity, but binds with a lower affinity to
unsaturated long- chain fatty acids. FABP2 may also help maintain energy homeostasis by
functioning as a lipid sensor
Organism class: human
UniProt ID: P12104
Gene: FABP2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
1. Velkov T, Chuang S, Wielens J, Sakellaris H, Charman WN, Porter CJ, Scanlon MJ: The
interaction of lipophilic drugs with intestinal fatty acid-binding protein. J Biol Chem.
2005 May 6;280(18):17769-76. Epub 2005 Feb 18. Pubmed
Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once
activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase
and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of
fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis
References:
1. Dill J, Patel AR, Yang XL, Bachoo R, Powell CM, Li S: A molecular mechanism for
ibuprofen-mediated RhoA inhibition in neurons. J Neurosci. 2010 Jan 20;30(3):963-72.
doi: 10.1523/JNEUROSCI.5045-09.2010. Pubmed
Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in
epithelial cells by regulating the SLC4A7 transporter
References:
1. Devor DC, Schultz BD: Ibuprofen inhibits cystic fibrosis transmembrane conductance
regulator-mediated Cl- secretion. J Clin Invest. 1998 Aug 15;102(4):679-87. Pubmed
Enzymes
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.
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
Actions: substrate
References:
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
References:
4. UDP-glucuronosyltransferase 1-1
Actions: substrate
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
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
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
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
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
Actions: inhibitor
May play an important role in regulating or promoting cell proliferation in some normal and
neoplastically transformed cells
References:
1. Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR,
Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal
anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012
Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. Pubmed
Actions: inhibitor
May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in
activity-dependent plasticity
References:
1. Palayoor ST, J-Aryankalayil M, Makinde AY, Cerna D, Falduto MT, Magnuson SR,
Coleman CN: Gene expression profile of coronary artery cells treated with nonsteroidal
anti-inflammatory drugs reveals off-target effects. J Cardiovasc Pharmacol. 2012
Jun;59(6):487-99. doi: 10.1097/FJC.0b013e31824ba6b5. Pubmed
Transporters
Actions: substrate
References:
Actions: substrate
References:
Actions: inhibitor
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
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
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
Actions: inhibitor
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
Actions: inhibitor
UniProt ID: Q4U2R8
Gene: hROAT1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
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
Actions: inhibitor
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
Actions: inhibitor
References:
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
References: