Identification

Name
Loxoprofen
Accession Number
DB09212
Type
Small Molecule
Groups
Investigational
Description

Loxoprofen (INN) is a non-steroidal anti-inflammatory drug in the propionic acid derivatives group, which also includes ibuprofen and naproxen, among others. It is marketed in Brazil, Mexico and Japan by Sankyo as its sodium salt, loxoprofen sodium, under the trade name Loxonin, Argentina as Oxeno and in India as Loxomac. It is available in these countries for oral administration, and a transdermal preparation was approved for sale in Japan in January 2006.

Structure
Thumb
Synonyms
Not Available
Product Ingredients
IngredientUNIICASInChI Key
Loxoprofen sodiumNDC2M7399S80382-23-6WORCCYVLMMTGFR-UHFFFAOYSA-M
International/Other Brands
Loxomac / Loxonin / Oxeno
Categories
UNII
3583H0GZAP
CAS number
68767-14-6
Weight
Average: 246.3016
Monoisotopic: 246.125594442
Chemical Formula
C15H18O3
InChI Key
YMBXTVYHTMGZDW-UHFFFAOYSA-N
InChI
InChI=1S/C15H18O3/c1-10(15(17)18)12-7-5-11(6-8-12)9-13-3-2-4-14(13)16/h5-8,10,13H,2-4,9H2,1H3,(H,17,18)
IUPAC Name
2-{4-[(2-oxocyclopentyl)methyl]phenyl}propanoic acid
SMILES
CC(C(O)=O)C1=CC=C(CC2CCCC2=O)C=C1

Pharmacology

Indication

Loxoprofen is non-steroidal anti-inflammatory medication (NSAID) indicated for pain and inflammation related to musculoskeletal and joint disorders [3]. In addition to its effects on pain, it is an antipyretic and anti-inflammatory medication [4].

Pharmacodynamics

Loxoprofen is a non-selective inhibitor of cyclooxygenase (prostaglandin endoperoxide synthase) enzyme, which is responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid [4, 5].

Mechanism of action

Loxoprofen is a prodrug of mefenamic acid and an inhibitor of the cyclooxygenase. Cyclooxygenase (COX) is present in 2 forms, including COX 1 and COX 2. Loxoprofen, a prodrug, is converted to its trans-alcohol active metabolite, by reduction of its cyclopentanone moiety[7].

Mefenamic acid, the active metabolite of Loxoprofen, is a powerful inhibitor of prostaglandin synthesis in vitro. Prostaglandins potentiate the action of bradykinin, which induces the sensation of pain[5].

COX 1 is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation [5]. COX 2 is induced in human cells post-injury or other stimuli, and is triggered to appear in large quantities at the sites of injury/stimuli [5].

The mechanism of action of Loxoprofen is to inhibit both COX 1 and 2, resulting in the inhibition of the above mediators, relieving symptoms of pain, inflammation, and fever [5].

TargetActionsOrganism
AProstaglandin G/H synthase 2
antagonist
Human
AProstaglandin G/H synthase 1
antagonist
Human
Absorption

Loxoprofen is rapidly and completely absorbed from the GI tract with a bioavailability of 95% [11]. The absorption phase of the medication occurs in the first 4-6 hours after ingestion. Food ingestion with the medication causes a slight decrease in the rate of loxoprofen absorption. [11].

Volume of distribution

Loxoprofen has a volume of distribution of 0.16 L/kg [11].

Protein binding

99% albumin-bound [11]. At doses of loxoprofen greater than 500 mg/day, an increased clearance of the drug occurs, as saturation of plasma protein binding occurs at higher doses [11].

Metabolism

Loxoprofen is a prodrug rapidly converted to its metabolite, mefenamic acid [12].

Route of elimination

50% renal excretion [10]. This drug is 20% - 30% excreted in the stool [7, 10].

Half life

The elimination half-life of Loxoprofen is approximately 15 hours [11].Steady concentration is achieved after 2-3 doses [11].

Clearance

Most of the drug as unchanged loxoprofen, 6-0-desmethyl loxoprofen (less than 1%) and glucuronide or other conjugates (66-92%) [10].

In patients with renal failure, metabolites may accumulate [11].

Toxicity

Adverse effects include anorexia, nausea, vomiting, bleeding, anemia, diahrrea, and constipation [10]. Loxoprofen toxicity may lead to gastrointestinal disturbance (including flatulence, dyspepsia and gastritis) and renal failure [11].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(4R)-limoneneThe risk or severity of adverse effects can be increased when (4R)-limonene is combined with Loxoprofen.
16-BromoepiandrosteroneThe risk or severity of adverse effects can be increased when Loxoprofen is combined with 16-Bromoepiandrosterone.
19-norandrostenedioneThe risk or severity of adverse effects can be increased when Loxoprofen is combined with 19-norandrostenedione.
5-androstenedioneThe risk or severity of adverse effects can be increased when Loxoprofen is combined with 5-androstenedione.
AbciximabThe risk or severity of bleeding and hemorrhage can be increased when Loxoprofen is combined with Abciximab.
AcebutololLoxoprofen may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of adverse effects can be increased when Loxoprofen is combined with Aceclofenac.
AcemetacinThe risk or severity of adverse effects can be increased when Loxoprofen is combined with Acemetacin.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Loxoprofen is combined with Acenocoumarol.
AcetaminophenLoxoprofen may decrease the excretion rate of Acetaminophen which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. Koup JR, Tucker E, Thomas DJ, Kinkel AW, Sedman AJ, Dyer R, Sharoky M: A single and multiple dose pharmacokinetic and metabolism study of meclofenamate sodium. Biopharm Drug Dispos. 1990 Jan-Feb;11(1):1-15. [PubMed:2322633]
  2. Loxoprofen [Link]
  3. MIMS LOXOPROFEN [Link]
  4. Mechanism of action of non steroidal anti-inflammatory drugs [Link]
  5. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks [Link]
  6. Loxoprofen Sodium, a Non-Selective NSAID, Reduces Atherosclerosis in Mice by Reducing Inflammation [Link]
  7. Comparison of Pharmacokinetics between Loxoprofen and Its Derivative with Lower Ulcerogenic Activity, Fluoro-loxoprofen [Link]
  8. Comparison of Pharmacokinetics between Loxoprofen and Its Derivative with Lower Ulcerogenic Activity, Fluoro-loxoprofen [Link]
  9. Aspirin, Non-Aspirin Nonsteroidal Anti-inflammatory Drugs, or Acetaminophen and risk of ovarian cancer [Link]
  10. LOXOPROFEN [Link]
  11. Loxoprofen Sodium [Link]
  12. Roxonin [Link]
External Links
Human Metabolome Database
HMDB0041920
KEGG Drug
D08149
PubChem Compound
3965
PubChem Substance
310265119
ChemSpider
3828
BindingDB
50140320
ChEBI
76172
ChEMBL
CHEMBL19299
PharmGKB
PA166049180
Wikipedia
Loxoprofen

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentChronic Non-specific, Uncomplicated Neck Pain1
2RecruitingTreatmentRheumatoid Arthritis1
2Unknown StatusTreatmentChronic Low Back Pain (CLBP)1
3CompletedTreatmentAcute Upper Respiratory Infection / Fevers1
3CompletedTreatmentLow Back Pain (LBP)1
3CompletedTreatmentPain1
3CompletedTreatmentPain / Traumas1
4CompletedTreatmentHealthy Volunteers1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)108.5 - 111[L1225]
boiling point (°C)220.7[L1225]
water solubility47 mg/mL[L1225]
Predicted Properties
PropertyValueSource
Water Solubility0.0663 mg/mLALOGPS
logP2.99ALOGPS
logP3.35ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.19ChemAxon
pKa (Strongest Basic)-7.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.37 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity68.8 m3·mol-1ChemAxon
Polarizability27.08 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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 phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Phenylpropanoic acids
Sub Class
Not Available
Direct Parent
Phenylpropanoic acids
Alternative Parents
Monocyclic monoterpenoids / Aromatic monoterpenoids / Benzene and substituted derivatives / Cyclic ketones / Monocarboxylic acids and derivatives / Carboxylic acids / Organic oxides / Hydrocarbon derivatives
Substituents
2-phenylpropanoic-acid / P-cymene / Aromatic monoterpenoid / Monocyclic monoterpenoid / Monoterpenoid / Monocyclic benzene moiety / Benzenoid / Ketone / Cyclic ketone / Monocarboxylic acid or derivatives
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
monocarboxylic acid, cyclopentanones (CHEBI:76172)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. KEGG DRUG: Loxoprofen [Link]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Loxoprofen sodium hydrate [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
Gene Name
PTGS2
Uniprot ID
P35354
Uniprot Name
Prostaglandin G/H synthase 2
Molecular Weight
68995.625 Da
References
  1. Loxoprofen sodium hydrate [Link]

Drug created on October 20, 2015 15:51 / Updated on October 01, 2018 16:36