FLURBIPROFEN AXETIL

Details

Stereochemistry	MIXED
Molecular Formula	C19H19FO4
Molecular Weight	330.3502
Optical Activity	UNSPECIFIED
Defined Stereocenters	0 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(OC(C)=O)OC(=O)C(C)C1=CC(F)=C(C=C1)C2=CC=CC=C2

InChI

InChIKey=ALIVXCSEERJYHU-UHFFFAOYSA-N

InChI=1S/C19H19FO4/c1-12(19(22)24-14(3)23-13(2)21)16-9-10-17(18(20)11-16)15-7-5-4-6-8-15/h4-12,14H,1-3H3

HIDE SMILES / InChI

Description
Sources: http://adisinsight.springer.com/drugs/800006253 | http://www.taisho-holdings.co.jp/en/release/2016/2016012001-e.pdf | https://www.ncbi.nlm.nih.gov/pubmed/16134939https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf | https://www.drugbank.ca/drugs/DB00712

Flurbiprofen, a propionic acid derivative, is a nonsteroidal anti-inflammatory drug that exhibits antiinflammatory, analgesic, and antipyretic activities in animal models. Flurbiprofen Tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis and for relief of the signs and symptoms of osteoarthritis. It may also be used to treat pain associated with dysmenorrhea and mild to moderate pain accompanied by inflammation (e.g. bursitis, tendonitis, soft tissue trauma). Flurbiprofen may also be used topically prior to ocular surgery to prevent or reduce intraoperative miosis. Similar to other NSAIAs, the anti-inflammatory effect of flurbiprofen occurs via reversible inhibition of cyclooxygenase (COX), the enzyme responsible for the conversion of arachidonic acid to prostaglandin G2 (PGG2) and PGG2 to prostaglandin H2 (PGH2) in the prostaglandin synthesis pathway. This effectively decreases the concentration of prostaglandins involved in inflammation, pain, swelling and fever. Flurbiprofen is a non-selective COX inhibitor and inhibits the activity of both COX-1 and -2. It is also one of the most potent NSAIAs in terms of prostaglandin inhibitory activity.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15336599	Inhibitor 8297	0.11 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24120370 \| https://www.ncbi.nlm.nih.gov/pubmed/15336599	Inhibitor 8297	6.46 µM [IC50]
Cyclooxygenase 89 Target ID: CHEMBL2094253 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26315084 \| https://www.selleckchem.com/products/flurbiprofen-axetil.html \| https://www.ncbi.nlm.nih.gov/pubmed/29540536	Inhibitor 8297
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16455248 \| https://www.ncbi.nlm.nih.gov/pubmed/16134939	Inhibitor 8297	0.2 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16134939	Inhibitor 8297	0.91 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Rheumatoid arthritis 316 Sources: https://www.drugs.com/pro/flurbiprofen-tablets.html	Primary	Approved 8429	Flurbiprofen Approved Use Flurbiprofen Tablets are indicated: • For relief of the signs and symptoms of rheumatoid arthritis. • For relief of the signs and symptoms of osteoarthritis. Launch Date 1988
Osteoarthritis 157 Sources: https://www.drugs.com/pro/flurbiprofen-tablets.html	Primary	Approved 8429	Flurbiprofen Approved Use Flurbiprofen Tablets are indicated: • For relief of the signs and symptoms of rheumatoid arthritis. • For relief of the signs and symptoms of osteoarthritis. Launch Date 1988
Osteoarthritis 157 Sources: http://www.taisho-holdings.co.jp/en/release/2016/2016012001-e.pdf	Primary	Approved 8429	LOQOA® Tape Approved Use LOQOA® Tape indicated for the treatment of osteoarthritis pain and inflammation. Launch Date 2015

C_max

Value	Dose	Co-administered	Analyte	Population
14 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19.67 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19808137	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
83 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
124.2 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19808137	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.5 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018766s015lbl.pdf	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
4.77 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19808137	150 mg single, oral dose: 150 mg route of administration: Oral experiment type: SINGLE co-administered:		FLURBIPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037	substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT3 642 MRP2 383 MRP4 204	CYP1A1 349 CYP2A6 543 CYP2B6 664 CYP2C19 991 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213

Drug as perpetrator

Target	Modality	Activity
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22072415/	yes [IC50 0.615 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/22072415/	yes [IC50 1.8 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26659924/	yes [IC50 10.6 uM]
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/26659924/	yes [IC50 58.4 uM]

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2A6 543	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/8937439/ Page: 3.0	no
UGT2B15 203	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 4.0	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT1A10 291	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15117964/ Page: 7.0	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes
UGT1A6 307	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/	yes
UGT1A7 236	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15117964/ Page: 7.0	yes
UGT1A8 283	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15117964/ Page: 7.0	yes
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT2B17 213	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 4.0	yes
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 1.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.ncbi.nlm.nih.gov/books/NBK537365/	yes	yes (co-administration study) Comment: Coadministration study with fluconazole (inhibitor of CYP2C9) increased AUCinf by 222%-299% after different visits of patients; Pharmacogenomic study: In patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin), reduce the dose of flurbiprofen to avoid abnormally high plasma levels due to reduced metabolic clearance Sources: https://www.ncbi.nlm.nih.gov/books/NBK537365/

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5130	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5130
ChemicalBook	CB7465967	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7465967
MolPort	MolPort-000-812-253	https://www.molport.com/shop/molecule-link/MolPort-000-812-253
eMolecules	538498	https://www.emolecules.com/cgi-bin/more?vid=538498

PubMed

Title	Date	PubMed
Estimation of acute flurbiprofen and ketoprofen toxicity in rat gastric mucosa at therapy-relevant doses.	2001 Dec	11822786
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients.	2001 Nov	11792017
Pathogenic importance of intestinal hypermotility in NSAID-induced small intestinal damage in rats.	2002	12379813
The effect of nonsteroidal antiinflammatory drugs ibuprofen, flurbiprofen, and diclofenac on in vitro and in vivo growth of mouse fibrosarcoma.	2002	12094544
[A simple method for determination of flurbiprofen in human plasma by gas chromatography-mass spectrometry].	2002 Apr	11995356
Affinity capillary electrophoresis using a low-concentration additive with the consideration of relative mobilities.	2002 Apr 15	11985325
In vitro release studies of flurbiprofen from different topical formulations.	2002 Aug	12236068
[The effectiveness of perioperative intravenous flurbiprofen in minor ear, neck and nose surgery].	2002 Aug	12229133
Dissection of metabolic, vascular, and nerve conduction interrelationships in experimental diabetic neuropathy by cyclooxygenase inhibition and acetyl-L-carnitine administration.	2002 Aug	12145179
Prostaglandin synthesis inhibitor affects humoral conditions and oxygen metabolism during normothermic cardiopulmonary bypass.	2002 Aug	12139494
Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application.	2002 Aug	12102196
Metabolic profile of NO-flurbiprofen (HCT1026) in rat brain and plasma: a LC-MS study.	2002 Aug 16	12127904
Rapid and simple quantitative assay method for diastereomeric flurbiprofen glucuronides in the incubation mixture.	2002 Aug 25	12127333
Therapeutic utility of aspirin in the ApcMin/+ murine model of colon carcinogenesis.	2002 Aug 9	12171603
Contractile effect of anaphylatoxin C5a and of a mimetic peptide on the human umbilical artery: further evidence for leukocyte-dependent vasomotion.	2002 Dec	12451314
Peripheral analgesic sites of action of anti-inflammatory drugs.	2002 Jul	12166614
Prevention by parenteral aspirin of indomethacin-induced gastric lesions in rats: mediation by salicylic acid.	2002 Jul	12141814
Flurbiprofen does not change the bispectral index and 95% spectral edge frequency during total intravenous anaesthesia with propofol and fentanyl.	2002 Jul	12113610
Characterization of the bone-resorptive effect of interleukin-11 in cultured mouse calvarial bones.	2002 Jul	12110441
The cannabinoids R(-)-7-hydroxy-delta-6-tetra-hydrocannabinol-dimethylheptyl (HU-210), 2-O-arachidonoylglycerylether (HU-310) and arachidonyl-2-chloroethylamide (ACEA) increase isoflurane provoked sleep duration by activation of cannabinoids 1 (CB1)-receptors in mice.	2002 Jul 5	12095655
Lipids and nitric oxide in porcine retinal and choroidal blood vessels.	2002 Jun	12099547
In vivo activation of N-methyl-D-aspartate receptors in the rat hippocampus increases prostaglandin E(2) extracellular levels and triggers lipid peroxidation through cyclooxygenase-mediated mechanisms.	2002 Jun	12065615
ATP can enhance the proton-induced CGRP release through P2Y receptors and secondary PGE(2) release in isolated rat dura mater.	2002 Jun	12044622
Prediction of poly(ethylene) glycol-drug eutectic compositions using an index based on the van't Hoff equation.	2002 Mar	11934239
Multidose flurbiprofen 8.75 mg lozenges in the treatment of sore throat: a randomised, double-blind, placebo-controlled study in UK general practice centres.	2002 Mar	11926713
Identification of drug-binding sites on human serum albumin using affinity capillary electrophoresis and chemically modified proteins as buffer additives.	2002 Mar	11920883
Nitric oxide-releasing drugs: a novel class of effective and safe therapeutic agents.	2002 May	12076987
Demonstration of dose response of flurbiprofen lozenges with the sore throat pain model.	2002 May	12011823
Mechanism of in vitro release kinetics of flurbiprofen loaded ethylcellulose micropellets.	2002 May-Jun	12230246
Drug therapy of urinary urge incontinence: a systematic review.	2002 Nov	12423868
Selective inhibition of Abeta42 production by NSAID R-enantiomers.	2002 Nov	12421374
Centrally administered galanin-like peptide modifies food intake in the rat: a comparison with galanin.	2002 Nov	12421338
Activation of CYP2C9-mediated metabolism by a series of dapsone analogs: kinetics and structural requirements.	2002 Nov	12386124
NO-flurbiprofen maintains duodenal blood flow, enhances mucus secretion contributing to lower mucosal injury.	2002 Nov	12381522
Kinetics of allopregnanolone formation catalyzed by human 3 alpha-hydroxysteroid dehydrogenase type III (AKR1C2).	2002 Nov 12	12416991
Biochemical stabilization enhances red blood cell recovery and stability following cryopreservation.	2002 Oct	12482381
Thermodynamic study of the enantiomeric resolution of flurbiprofen by HPLC using Chiralpak AD-RH column.	2002 Oct	12426948
Structure-function relationship and role of tumor necrosis factor-alpha-converting enzyme in the down-regulation of L-selectin by non-steroidal anti-inflammatory drugs.	2002 Oct 11	12147693
Efficient synthesis of alpha-aryl esters by room-temperature palladium-catalyzed coupling of aryl halides with ester enolates.	2002 Oct 23	12381200
A nitric oxide-donating flurbiprofen derivative reduces neuroinflammation without interacting with galantamine in the rat.	2002 Oct 25	12398920
Cyclooxygenase and 5-lipoxygenase inhibitors protect against mononuclear phagocyte neurotoxicity.	2002 Sep-Oct	12392782
Prostaglandin synthesis inhibitor prevents hypotension without impairing gut perfusion during normothermic cardiopulmonary bypass.	2002 Sep-Oct	12296570
Aging Enables Ca2+ Overload and Apoptosis Induced by Amyloid-β Oligomers in Rat Hippocampal Neurons: Neuroprotection by Non-Steroidal Anti-Inflammatory Drugs and R-Flurbiprofen in Aging Neurons.	2016 Jul 22	27447424
Analgesic effect of different dosage of Flurbiprofen axetil in laparoscopic cholecystectomy in comparison with other analgesic drugs.	2017 Sep	29084663
Population pharmacokinetic modeling of flurbiprofen, the active metabolite of flurbiprofen axetil, in Chinese patients with postoperative pain.	2018	30555252
Intraoperative administration of intravenous flurbiprofen axetil with nalbuphine reduces postoperative pain after orbital decompression: a single-center, prospective randomized controlled trial.	2019	30863138
[Effect of Flurbiprofen Axetil on Low-frequency Fluctuation Amplitude of Resting-state Functional Magnetic Resonance Imaging in Trigeminal Neuralgia].	2019 Apr 28	31060679
Effect of flurbiprofen axetil on postoperative delirium for elderly patients.	2019 Jun	31007001
[Effect of multimodal analgesia using periprostatic nerve block anesthesia combined with flurbiprofen in transperineal template-guided prostate biopsy].	2019 Jun 1	31142067
[Postoperative low-dose sufentanil combined with transversus abdominis plane block promotes recovery following laparoscopic hysterectomy].	2019 Mar 30	31068298

Patents

Sample Use Guides

In Vivo Use Guide

Loqoa® is available as a patch formulation, containing 40 mg of Esflurbiprofen. The recommended dose is applied to the lesion area once daily. Do not apply more than two patches simultaneously.

Route of Administration: Topical

In Vitro Use Guide

At 100 uM concentration Esflurbiprofen (S-Flurbiprofen) demonstrated 37% inhibition of Abeta42 in SH-SY5Y cells and 65% in HEK cells.

Name

Type

Language

FLURBIPROFEN AXETIL

Common Name

English

(1,1'-BIPHENYL)-4-ACETIC ACID, 2-FLUORO-.ALPHA.-METHYL-, 1-(ACETYLOXY)ETHYL ESTER

Common Name

English

ROPION

Brand Name

English

FP-83

Code

English

LFP 83

Code

English

FP 83

Code

English

FLURBIPROFEN AXETIL [JAN]

Common Name

English

Flurbiprofen axetil [WHO-DD]

Common Name

English

LFP-83

Code

English

Code System Code Type Description

EPA CompTox

DTXSID8048600