Loxoprofen

Identification

Summary

Loxoprofen is an NSAID used to treat pain and inflammation in musculoskeletal conditions.

Generic Name

Loxoprofen

DrugBank Accession Number

DB09212

Background

Loxoprofen is a propionic acid derivative non-steroidal anti-inflammatory drug. It is marketed under the trade name Loxonin in Brazil, Mexico and Japan by Sankyo, as Loxomac in India, and as Oxeno in Argentina. A transdermal preparation was approved for use in Japan in January 2006.

Type

Small Molecule

Groups

Approved

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Loxoprofen (DB09212)

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Weight

Average: 246.3016
Monoisotopic: 246.125594442

Chemical Formula

C₁₅H₁₈O₃

Synonyms

• Loxoprofen
• Loxoprofene
• Loxoprofeno
• Loxoprofenum

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Pharmacology

Indication

Loxoprofen is non-steroidal anti-inflammatory medication (NSAID) indicated for pain and inflammation related to musculoskeletal and joint disorders.⁶ In addition to its effects on pain, it is an antipyretic and anti-inflammatory medication.⁷

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Associated Conditions

Indication Type	Indication	Combined Product Details	Approval Level	Age Group	Patient Characteristics	Dose Form
Treatment of	Orthopaedic related pain (musculoskeletal pain)		••••••••••••			••••••
Treatment of	Orthopaedic related pain (musculoskeletal pain)		••••••••••••			•••
Treatment of	Rheumatism		••••••••••••			••••••
Treatment of	Rheumatism		••••••••••••			•••
Treatment of	Soft tissue injury		••••••••••••			••••••

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Contraindications & Blackbox Warnings

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Pharmacodynamics

Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid.^7,8

Mechanism of action

Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase.³ Cyclooxygenase (COX) is present in 2 forms, COX-1 and COX-2, with each serving different functions. COX-1 is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation.⁸ COX-2 is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain.⁸

Loxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc).⁸

Target	Actions	Organism
AProstaglandin G/H synthase 2	antagonist	Humans
AProstaglandin G/H synthase 1	antagonist	Humans

Absorption

Loxoprofen is rapidly and completely absorbed from the GI tract with a bioavailability of 95%.¹⁴ 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.¹⁴

Volume of distribution

Loxoprofen has a volume of distribution of 0.16 L/kg.¹⁴

Protein binding

99% albumin-bound.¹⁴ At doses of loxoprofen greater than 500 mg/day, clearance of the drug increases as saturation of plasma protein binding occurs at higher doses.¹⁴

Metabolism

Loxoprofen is a prodrug that is rapidly converted to its active trans-alcohol metabolite by carbonyl reductase in the liver.² This same process also results in a cis-alcohol metabolite, though this isomer carries little pharmacological activity.^1,3 The parent drug has also been observed to undergo oxidation via CYP3A4/5 to two hydroxylated metabolites (M3 and M4) and glucuronidation by UGT2B7 to two glucuronide metabolites (M5 and M6).¹ The alcohol metabolites of loxoprofen also undergo glucuronide conjugation via UGT2B7 to two glucuronide metabolites (M7 and M8) prior to excretion.¹

When applied in topical formulations, loxoprofen is metabolized to its active trans-alcohol form by carbonyl reductase in the skin.⁴

Hover over products below to view reaction partners

• Loxoprofen
  • Loxoprofen trans-OH metabolite
  • Loxoprofen cis-OH metabolite

Route of elimination

50% renal excretion.¹³ This drug is 20% - 30% excreted in the stool.^10,13

Half-life

The elimination half-life of Loxoprofen is approximately 15 hours.¹⁴ Steady concentration is achieved after 2-3 doses.¹⁴

Clearance

Most of the drug as unchanged loxoprofen, 6-0-desmethyl loxoprofen (less than 1%) and glucuronide or other conjugates (66-92%).¹³

In patients with renal failure, metabolites may accumulate.¹⁴

Adverse Effects

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Toxicity

Adverse effects include anorexia, nausea, vomiting, bleeding, anemia, diarrhea, and constipation.¹³ Loxoprofen toxicity may lead to gastrointestinal disturbance (including flatulence, dyspepsia and gastritis) and renal failure.¹⁴

Pathways

Not Available

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Not Available

Interactions

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This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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Abacavir	Loxoprofen may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abciximab	The risk or severity of bleeding and hemorrhage can be increased when Loxoprofen is combined with Abciximab.
Acebutolol	Loxoprofen may decrease the antihypertensive activities of Acebutolol.
Aceclofenac	The risk or severity of adverse effects can be increased when Aceclofenac is combined with Loxoprofen.
Acemetacin	The risk or severity of adverse effects can be increased when Loxoprofen is combined with Acemetacin.

Food Interactions

• Exercise caution with grapefruit products. Loxoprofen is metabolized by CYP3A4 to an inactive metabolite and grapefruit is a CYP3A4 inhibitor.
• Exercise caution with St. John's Wort. Loxoprofen is metabolized by CYP3A4 to an inactive metabolite and St. Johns Wort is a CYP3A4 inducer.
• Take with food. Taking loxoprofen with food may reduce the risk of gastrointestinal upset.

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Product Ingredients

Ingredient	UNII	CAS	InChI Key
Loxoprofen sodium	NDC2M7399S	80382-23-6	WORCCYVLMMTGFR-UHFFFAOYSA-M

International/Other Brands

Loxomac / Loxonin / Oxeno

Categories

ATC Codes

M02AA31 — Loxoprofen

• M02AA — Antiinflammatory preparations, non-steroids for topical use
• M02A — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
• M02 — TOPICAL PRODUCTS FOR JOINT AND MUSCULAR PAIN
• M — MUSCULO-SKELETAL SYSTEM

Drug Categories

• Acids, Carbocyclic
• Agents causing hyperkalemia
• Agents that produce hypertension
• Analgesics
• Analgesics, Non-Narcotic
• Anti-Inflammatory Agents
• Anti-Inflammatory Agents, Non-Steroidal
• Antiinflammatory Preparations, Non-Steroids for Topical Use
• Antirheumatic Agents
• Musculo-Skeletal System
• Nephrotoxic agents
• Non COX-2 selective NSAIDS
• Peripheral Nervous System Agents
• Sensory System Agents
• Topical Products for Joint and Muscular Pain
• UGT2B7 substrates

Chemical TaxonomyProvided by Classyfire

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 / Aromatic homomonocyclic compound / Aromatic monoterpenoid / Benzenoid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative / Cyclic ketone / Hydrocarbon derivative / Ketone

Molecular Framework

Aromatic homomonocyclic compounds

External Descriptors

monocarboxylic acid, cyclopentanones (CHEBI:76172)

Affected organisms

Not Available

Chemical Identifiers

UNII

3583H0GZAP

CAS number

68767-14-6

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

References

General References

1. Shrestha R, Cho PJ, Paudel S, Shrestha A, Kang MJ, Jeong TC, Lee ES, Lee S: Exploring the Metabolism of Loxoprofen in Liver Microsomes: The Role of Cytochrome P450 and UDP-Glucuronosyltransferase in Its Biotransformation. Pharmaceutics. 2018 Aug 2;10(3). pii: pharmaceutics10030112. doi: 10.3390/pharmaceutics10030112. [Article]
2. Quinones-Lombrana A, Li N, Del Solar V, Atilla-Gokcumen GE, Blanco JG: CBR1 rs9024 genotype status impacts the bioactivation of loxoprofen in human liver. Biopharm Drug Dispos. 2018 Jun;39(6):315-318. doi: 10.1002/bdd.2135. [Article]
3. Riendeau D, Salem M, Styhler A, Ouellet M, Mancini JA, Li CS: Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2. Bioorg Med Chem Lett. 2004 Mar 8;14(5):1201-3. [Article]
4. Sawamura R, Sakurai H, Wada N, Nishiya Y, Honda T, Kazui M, Kurihara A, Shinagawa A, Izumi T: Bioactivation of loxoprofen to a pharmacologically active metabolite and its disposition kinetics in human skin. Biopharm Drug Dispos. 2015 Sep;36(6):352-363. doi: 10.1002/bdd.1945. Epub 2015 Apr 21. [Article]
5. Loxoprofen [Link]
6. MIMS LOXOPROFEN [Link]
7. Mechanism of action of non steroidal anti-inflammatory drugs [Link]
8. Non-Steroidal Anti-Inflammatory Drugs: An Overview of Cardiovascular Risks [Link]
9. Loxoprofen Sodium, a Non-Selective NSAID, Reduces Atherosclerosis in Mice by Reducing Inflammation [Link]
10. Comparison of Pharmacokinetics between Loxoprofen and Its Derivative with Lower Ulcerogenic Activity, Fluoro-loxoprofen [Link]
11. Comparison of Pharmacokinetics between Loxoprofen and Its Derivative with Lower Ulcerogenic Activity, Fluoro-loxoprofen [Link]
12. Aspirin, Non-Aspirin Nonsteroidal Anti-inflammatory Drugs, or Acetaminophen and risk of ovarian cancer [Link]
13. LOXOPROFEN [Link]
14. Loxoprofen Sodium [Link]
15. Roxonin [Link]

External Links

Human Metabolome Database

HMDB0041920

KEGG Drug

D08149

PubChem Compound

3965

PubChem Substance

310265119

ChemSpider

3828

BindingDB

50140320

RxNav

28908

ChEBI

76172

ChEMBL

CHEMBL19299

PharmGKB

PA166049180

Wikipedia

Loxoprofen

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Ankylosing Spondylitis (AS)	1
4	Completed	Treatment	Healthy Subjects (HS)	1
3	Completed	Treatment	Acute Upper Respiratory Infections / Fever	1
3	Completed	Treatment	Back Pain Lower Back	1
3	Completed	Treatment	Lumbar Spine Disc Herniation	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Gel	Topical	1 %
Tablet	Oral	60.000 mg
Patch	Topical	100 mg
Tablet	Oral	60 mg
Patch	Transdermal	100 mg

Prices

Not Available

Patents

Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	108.5 - 111	Not Available
boiling point (°C)	220.7	Not Available
water solubility	47 mg/mL	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0663 mg/mL	ALOGPS
logP	2.99	ALOGPS
logP	3.35	Chemaxon
logS	-3.6	ALOGPS
pKa (Strongest Acidic)	4.19	Chemaxon
pKa (Strongest Basic)	-7.4	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	3	Chemaxon
Hydrogen Donor Count	1	Chemaxon
Polar Surface Area	54.37 Å2	Chemaxon
Rotatable Bond Count	4	Chemaxon
Refractivity	68.8 m3·mol-1	Chemaxon
Polarizability	27.08 Å3	Chemaxon
Number of Rings	2	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	splash10-0gi0-2950000000-f1f143e2589e1aea4173
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-00or-0890000000-103c4949f70434b3304a
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0uxr-0690000000-2e8f78eff83b04fe6c5a
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0uyi-3790000000-61e5153ffb5a4903a6f7
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0gdi-1980000000-9124d0a28e7a84fa923e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0gi0-2930000000-f34629c393424d98a942
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0gc0-0900000000-07456f7e14a33ff22a0a
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å2)	Source type	Source
[M-H]-	168.8326816	predicted	DarkChem Lite v0.1.0
[M-H]-	156.52101	predicted	DeepCCS 1.0 (2019)
[M+H]+	170.1009816	predicted	DarkChem Lite v0.1.0
[M+H]+	158.879	predicted	DeepCCS 1.0 (2019)
[M+Na]+	168.8866816	predicted	DarkChem Lite v0.1.0
[M+Na]+	164.97214	predicted	DeepCCS 1.0 (2019)

Targets

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Details1. Prostaglandin G/H synthase 2

Kind

Protein

Organism

Humans

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. Riendeau D, Salem M, Styhler A, Ouellet M, Mancini JA, Li CS: Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2. Bioorg Med Chem Lett. 2004 Mar 8;14(5):1201-3. [Article]

Details2. Prostaglandin G/H synthase 1

Kind

Protein

Organism

Humans

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

References

1. Riendeau D, Salem M, Styhler A, Ouellet M, Mancini JA, Li CS: Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2. Bioorg Med Chem Lett. 2004 Mar 8;14(5):1201-3. [Article]

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Drug created at October 20, 2015 21:51 / Updated at February 02, 2024 22:52