DEXKETOPROFEN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H14O3
Molecular Weight	254.2806
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@H](C(O)=O)C1=CC(=CC=C1)C(=O)C2=CC=CC=C2

InChI

InChIKey=DKYWVDODHFEZIM-NSHDSACASA-N

InChI=1S/C16H14O3/c1-11(16(18)19)13-8-5-9-14(10-13)15(17)12-6-3-2-4-7-12/h2-11H,1H3,(H,18,19)/t11-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21052564https://www.drugs.com/international/dexketoprofen.html
Curator's Comment: The description was created based on several sources, including https://clinicaltrials.gov/ct2/show/NCT02159547 | https://www.ncbi.nlm.nih.gov/pubmed/28540716 | https://clinicaltrials.gov/ct2/show/NCT03122314 | https://www.ncbi.nlm.nih.gov/pubmed/28326850 | https://clinicaltrials.gov/ct2/show/NCT02092012

Dexketoprofen is a nonsteroidal anti-inflammatory drug (NSAID), manufactured by Menarini under the tradename Keral. Dexketoprofen is indicated for short-term treatment of mild to moderate pain, including dysmenorrhoea. Dexketoprofen works by blocking the action of a substance in the body called cyclo-oxygenase, which is involved in the production of chemicals in the body called prostaglandins. Prostaglandins are produced in response to injury or certain diseases and would otherwise go on to cause swelling, inflammation, and pain. By blocking cyclo-oxygenase, dexketoprofen prevents the production of prostaglandins and therefore reduces inflammation and pain. Along with peripheral analgesic action, it possesses central analgesic action. Dexketoprofen may cause dizziness, and patients should not, therefore, drive or operate heavy machinery or vehicles until they are familiar with how dexketoprofen affects them. Concomitant use of alcohol and other sedatives may potentiate this effect. In a small subset of individuals, the dizziness may be intolerable and require the transition to an alternative treatment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10841807	Inhibitor 8297	1.9 nM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10841807	Inhibitor 8297	27.0 nM [IC50]
Interleukin-8 receptors, CXCR1/CXCR2 6 Target ID: CHEMBL2096909 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15974585	Antagonist 2778	50.0 nM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14510637	Inhibitor 8297	0.52 µM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14510637	Inhibitor 8297	0.019 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pain, postoperative 9 Sources: https://clinicaltrials.gov/ct2/show/NCT02568735	Primary	Approved 8429	Keral Approved Use Unknown
Migraine 103 Sources: https://clinicaltrials.gov/ct2/show/NCT02159547	Primary	Approved 8429	Keral Approved Use Unknown
Musculoskeletal pain 10 Sources: https://clinicaltrials.gov/ct2/show/NCT03122314	Primary	Approved 8429	Keral Approved Use Unknown
Pain 614 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2c99853-1268-4998-a44b-2bf0c0b70fd2	Primary	Approved 8429	KETOPROFEN Approved Use Ketoprofen capsules USP are indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ketoprofen capsules USP are indicated for the management of pain. Ketoprofen capsules USP are also indicated for treatment of primary dysmenorrhea. Launch Date 1992
Primary dysmenorrhea 16 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2c99853-1268-4998-a44b-2bf0c0b70fd2	Primary	Approved 8429	KETOPROFEN Approved Use Ketoprofen capsules USP are indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ketoprofen capsules USP are indicated for the management of pain. Ketoprofen capsules USP are also indicated for treatment of primary dysmenorrhea. Launch Date 1992
Rheumatoid arthritis 316 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2c99853-1268-4998-a44b-2bf0c0b70fd2	Primary	Approved 8429	KETOPROFEN Approved Use Ketoprofen capsules USP are indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ketoprofen capsules USP are indicated for the management of pain. Ketoprofen capsules USP are also indicated for treatment of primary dysmenorrhea. Launch Date 1992
Osteoarthritis 157 Sources: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c2c99853-1268-4998-a44b-2bf0c0b70fd2	Primary	Approved 8429	KETOPROFEN Approved Use Ketoprofen capsules USP are indicated for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ketoprofen capsules USP are indicated for the management of pain. Ketoprofen capsules USP are also indicated for treatment of primary dysmenorrhea. Launch Date 1992

C_max

Value	Dose	Co-administered	Analyte	Population
10.1 μg/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7439263	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		KETOPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
21.91 μg × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7439263	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		KETOPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.13 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7439263	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		KETOPROFEN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
12.5 mg single, oral Dose: 12.5 mg Route: oral Route: single Dose: 12.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022470s000medr.pdf Page: p. 34	unhealthy, 36.8 years (range: 18 - 65 years) n = 90 Health Status: unhealthy Age Group: 36.8 years (range: 18 - 65 years) Sex: M+F Population Size: 90 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022470s000medr.pdf Page: p. 34	Disc. AE: Rash... AEs leading to discontinuation/dose reduction: Rash (mild, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022470s000medr.pdf Page: p. 34
2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019816s011lbl.pdf	unhealthy, 45 years Health Status: unhealthy Age Group: 45 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019816s011lbl.pdf	Other AEs: Epigastric pain... Other AEs: Epigastric pain (mild, 1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019816s011lbl.pdf
100 mg 1 times / day multiple, topical Dose: 100 mg, 1 times / day Route: topical Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16078335/	unhealthy, adult n = 172 Health Status: unhealthy Condition: tendinitis Age Group: adult Population Size: 172 Sources: https://pubmed.ncbi.nlm.nih.gov/16078335/	Sources: https://pubmed.ncbi.nlm.nih.gov/16078335/
100 ug 3 times / day steady, oral (max) Dose: 100 ug, 3 times / day Route: oral Route: steady Dose: 100 ug, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	unhealthy n = 50 Health Status: unhealthy Condition: Lymphedema Population Size: 50 Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	Other AEs: Cellulitis... Other AEs: Cellulitis (below serious, 3 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT02257970
75 ug 3 times / day steady, oral Dose: 75 ug, 3 times / day Route: oral Route: steady Dose: 75 ug, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	unhealthy n = 19 Health Status: unhealthy Condition: Lymphedema Population Size: 19 Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	Other AEs: Rash... Other AEs: Rash (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02257970
75 ug 3 times / day steady, oral Dose: 75 ug, 3 times / day Route: oral Route: steady Dose: 75 ug, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	unhealthy n = 23 Health Status: unhealthy Condition: Lymphedema Population Size: 23 Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	Other AEs: Cellulitis... Other AEs: Cellulitis (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT02257970

AEs

AE	Significance	Dose	Population
Rash	mild, 1 patient Disc. AE	12.5 mg single, oral Dose: 12.5 mg Route: oral Route: single Dose: 12.5 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022470s000medr.pdf Page: p. 34	unhealthy, 36.8 years (range: 18 - 65 years) n = 90 Health Status: unhealthy Age Group: 36.8 years (range: 18 - 65 years) Sex: M+F Population Size: 90 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022470s000medr.pdf Page: p. 34
Epigastric pain	mild, 1 patient	2400 mg single, oral Overdose Dose: 2400 mg Route: oral Route: single Dose: 2400 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019816s011lbl.pdf	unhealthy, 45 years Health Status: unhealthy Age Group: 45 years Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/019816s011lbl.pdf
Cellulitis	below serious, 3 patients	100 ug 3 times / day steady, oral (max) Dose: 100 ug, 3 times / day Route: oral Route: steady Dose: 100 ug, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	unhealthy n = 50 Health Status: unhealthy Condition: Lymphedema Population Size: 50 Sources: https://clinicaltrials.gov/ct2/show/NCT02257970
Rash	below serious, 1 patient	75 ug 3 times / day steady, oral Dose: 75 ug, 3 times / day Route: oral Route: steady Dose: 75 ug, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	unhealthy n = 19 Health Status: unhealthy Condition: Lymphedema Population Size: 19 Sources: https://clinicaltrials.gov/ct2/show/NCT02257970
Cellulitis	below serious, 1 patient	75 ug 3 times / day steady, oral Dose: 75 ug, 3 times / day Route: oral Route: steady Dose: 75 ug, 3 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT02257970	unhealthy n = 23 Health Status: unhealthy Condition: Lymphedema Population Size: 23 Sources: https://clinicaltrials.gov/ct2/show/NCT02257970

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 599 OAT2 145 OAT3 642 OAT4 146 MRP2 383 MRP4 204	CYP 270 UGT1A1 418 UGT1A3 422 UGT1A9 380 UGT2B4 249 UGT2B7 389

Drug as perpetrator

Target	Modality	Activity
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/10991954/	yes [IC50 1.3 uM]
MRP2 475	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17005917/	yes [IC50 1.4 uM]
MRP4 238	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/17005917/	yes [IC50 11.9 uM]
OAT2 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 400 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 5.98 uM]
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/12388633/	yes [IC50 70.3 uM]

Drug as victim

Target	Modality	Activity
CYP 270	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19422321/ Page: 2.0	minor
UGT2B4 249	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 8.0	no
UGT1A1 418	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 8.0	yes
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 8.0	yes
UGT1A9 380	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 8.0	yes
UGT2B7 389	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15843492/ Page: 8.0	yes

PubMed

Title	Date	PubMed
Iatrogenic cost factors incorporating mild and moderate adverse events in the economic comparison of aceclofenac and other NSAIDs.	2001	11548913
Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease.	2001	11511027
Use of continuous fluid drainage for severe polyhydramnios due to twin to twin transfusion syndrome.	2001	11491373
[Two complex suicidal poisonings with drugs and their medicolegal aspects].	2001	11450365
Early-morning administration of dexketoprofen-trometamol in morning stiffness induced by nodal osteoarthritis of the hands.	2001	11447775
Release behavior of ketoprofen from poly(acryloyl-L-proline methyl ester) gels having different crosslinked networks.	2001	11416991
Overdose of ketoprofen could be dangerous.	2001 Apr	11573649
Interaction between the antinociceptive effect of ketoprofen and adrenergic modulatory systems.	2001 Aug	11580099
Simultaneous optimization based on artificial neural networks in ketoprofen hydrogel formula containing O-ethyl-3-butylcyclohexanol as percutaneous absorption enhancer.	2001 Aug	11536204
Binding constant determination of drugs toward subdomain IIIA of human serum albumin by near-infrared dye-displacement capillary electrophoresis.	2001 Aug	11519955
Investigation of the utility of an in vitro release test for optimizing semisolid dosage forms.	2001 Aug	11485188
Sustained release ketoprofen microparticles with ethylcellulose and carboxymethylethylcellulose.	2001 Aug 10	11489315
In vitro distribution of ketoprofen enantiomers in articular tissues of osteoarthritic patients.	2001 Dec	11600284
Oral ketoprofen in children--could it have been done differently?	2001 Jan	11575403
Cytokines and cytokine inducers stimulate prostaglandin E2 entry into the brain.	2001 Jul	11510884
Comparison of tissue concentrations after intramuscular and topical administration of ketoprofen.	2001 Jul	11496958
[Enantiomeric separation of drugs based on macrocyclic antibiotics].	2001 Jul	11475888
Analgesic profile of peroral and topical ketoprofen upon low pH-induced muscle pain.	2001 Jul	11406335
Enantioselective inhibition of the binding of rac-profens to human serum albumin induced by lithocholate.	2001 Jul	11400191
Evaluation of percutaneous absorption and skin irritation of ketoprofen through rat skin: in vitro and in vivo study.	2001 Jul 17	11427353
Stereoselective pharmacokinetics of ketoprofen in llamas following intravenous administration.	2001 Jun	11442802
Enantiospecific pharmacokinetics of ketoprofen in plasma and synovial fluid of horses with acute synovitis.	2001 Jun	11442795
Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery.	2001 Jun	11400845
Simultaneous photocontact sensitivity to ketoprofen and oxybenzone.	2001 Jun	11380553
Simultaneous determination of loxoprofen and its diastereomeric alcohol metabolites in human plasma and urine by a simple HPLC-UV detection method.	2001 Jun	11377045
Intercalation compounds of hydrotalcite-like anionic clays with antiinflammatory agents--I. Intercalation and in vitro release of ibuprofen.	2001 Jun 4	11376964
[Acute pancreatitis and ketoprofen].	2001 Jun-Jul	11673744
[Ketoprofen-induced acute hepatitis].	2001 Jun-Jul	11673741
I.v. ketoprofen for analgesia after tonsillectomy: comparison of pre- and post-operative administration.	2001 Mar	11573528
Thoracoscopy as a nonpharmacotherapeutic research modification for limiting postoperative chest pain.	2001 Mar-Apr	11396618
Effect of oxidative stress on the structure and function of human serum albumin.	2001 May	11465418
Chiral resolution of flurbiprofen and ketoprofen enantiomers by HPLC on a glycopeptide-type column chiral stationary phase.	2001 May	11391680
Screening procedure for detection of non-steroidal anti-inflammatory drugs and their metabolites in urine as part of a systematic toxicological analysis procedure for acidic drugs and poisons by gas chromatography-mass spectrometry after extractive methylation.	2001 May-Jun	11386636
Onset of analgesia for liquigel ibuprofen 400 mg, acetaminophen 1000 mg, ketoprofen 25 mg, and placebo in the treatment of postoperative dental pain.	2001 Nov	11697757
Measurement of ketoprofen in horse urine using gas chromatography-mass spectrometry.	2001 Oct	11696081
Influence of betacyclodextrin on the release of poorly soluble drugs from inert and hydrophilic heterogeneous polymeric matrices.	2001 Oct	11519784
Lipopolysaccharide-induced increase of prostaglandin E(2) is mediated by inducible nitric oxide synthase activation of the constitutive cyclooxygenase and induction of membrane-associated prostaglandin E synthase.	2001 Oct 1	11564815
Effects of diclofenac and ketoprofen on nerve conduction velocity in experimental nerve root compression.	2001 Oct 15	11598507
Optimized conditions of bio-mimetic artificial membrane permeation assay.	2001 Oct 9	11576780
Transdermal delivery of ketoprofen using microemulsions.	2001 Oct 9	11576778
[ Ambulatory laparoscopic gynecological surgery in Africa: feasibility].	2001 Sep	11598560
Efficacy and safety of ketoprofen lysine salt mouthwash versus benzydamine hydrochloride mouthwash in acute pharyngeal inflammation: a randomized, single-blind study.	2001 Sep	11589263
Comparison of the effects of ketoprofen on platelet function in the presence and absence of aspirin.	2001 Sep	11566459
Promoting mechanism of menthol derivative, 1-O-ethyl-3-buthylcyclohexanol, on the percutaneous absorption of ketoprofen.	2001 Sep	11558566
Incompatibility of prochlorperizine and ketoprofen.	2001 Sep	11550690
Photocontact dermatitis to ketoprofen.	2001 Sep	11526526
Antihyperalgesic effects of the muscarinic receptor ligand vedaclidine in models involving central sensitization in rats.	2001 Sep	11514081
Functional characterization of rat organic anion transporter 2 in LLC-PK1 cells.	2001 Sep	11504818
In vitro and in vivo evaluation of polyoxyethylene esters as dermal prodrugs of ketoprofen, naproxen and diclofenac.	2001 Sep	11500258
Enhancement of the activity of doxorubicin by inhibition of glutamate transporter.	2001 Sep 15	11641044

Patents

Sample Use Guides

In Vivo Use Guide

Rheumatoid Arthritis and Osteoarthritis: 75 mg three times or 50 mg four times a day. The recommended maximum daily dose of ketoprofen capsules is 300 mg/day. Pain and Dysmenorrhea: 25 to 50 mg every 6 to 8 hours as necessary.

Route of Administration: Oral

In Vitro Use Guide

5 mM Ketoprofen (mouse isolated epidermal cells)

Name

Type

Language

DEXKETOPROFEN

Official Name

English

ARVELES

Brand Name

English

dexketoprofen [INN]

Common Name

English

BENZENEACETIC ACID, 3-BENZOYL-.ALPHA.-METHYL-, (.ALPHA.S)-

Systematic Name

English

BENZENEACETIC ACID, 3-BENZOYL-.ALPHA.-METHYL-, (S)-

Common Name

English

Dexketoprofen [WHO-DD]

Common Name

English

(S)-2-(3-BENZOYLPHENYL)PROPANOIC ACID

Systematic Name

English

(S)-KETOPROFEN

Common Name

English

(.ALPHA.S)-3-BENZOYL-.ALPHA.-METHYLBENZENEACETIC ACID

Common Name

English

(2S)-2-(3-BENZOYLPHENYL)PROPIONIC ACID

Systematic Name

English

(+)-KETOPROFEN

Common Name

English

(+)-2-(3-BENZOYLPHENYL)PROPIONIC ACID

Systematic Name

English

(+)-(S)-M-BENZOYLHYDRATROPIC ACID

Systematic Name

English

(S)-(+)-2-(3-BENZOYLPHENYL)PROPIONIC ACID

Systematic Name

English

KETOPROFEN, (S)-

Common Name

English

HYDRATROPIC ACID, M-BENZOYL-, (+)-

Common Name

English

Classification Tree Code System Code

WHO-ATC

M02AA27