Bufexamac

Identification

Summary

Bufexamac is an NSAID used to treat skin conditions like atopic eczema and inflammatory dermatoses.

Generic Name
Bufexamac
DrugBank Accession Number
DB13346
Background

Bufexamac is a non-steroidal anti-inflammatory drug (NSAID) under the market name Droxaryl, Malipuran, Paraderm and Parfenac. It is typically administered topically for the treatment of subacute and chronic eczema of the skin, including atopic eczema and other inflammatory dermatoses, as well as sunburn and other minor burns, and itching. It has also been used in suppositories in combination with local anaesthetics indicated for haemorrhoids. The use of bufexamac has been discontinued in Canada and the United States, which may be due to undetermined clinical efficacy and a high prevalence of contact sensitization 2. Bufexamac was also withdrawn by the EMA in April 2010.

Type
Small Molecule
Groups
Approved, Withdrawn
Structure
Thumb
Weight
Average: 223.272
Monoisotopic: 223.120843411
Chemical Formula
C12H17NO3
Synonyms
  • 2-(p-Butoxyphenyl)-acetohydroxamic acid
  • 4-Butoxy-N-hydroxybenzeneacetamide
  • 4-Butoxyphenylacetohydroxamic acid
  • Acide p-butoxyphenylacethydroxamique
  • Bufexamac
  • bufexamaco
  • bufexamacum
  • Bufexamic acid
  • p-Butoxyphenylacetohydroxamic acid
External IDs
  • CP 1044 J3
  • CP-1044-J3

Pharmacology

Indication

Indicated for the treatment of various skin conditions, such as atopic eczema and other inflammatory dermatoses.

Pharmacology
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Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Bufexamac is a topically-active anti-inflammatory agent that inhibits the cyclooxygenase enzyme. In cutaneous and deep experimental inflammation, topical administration of bufexamac exerted a dose-related anti-inflammatory effect 1. In guinea pigs, bufexamax was shown to be more active than topical acetylsalicylic acid 5% or phenylbutazone 5% in delaying the local increase in temperature resulting from UV exposure 1. Bufexamac is unlikely to have any effect on wound healing 1.

Mechanism of action

The full mechanism of action is unclear. It is proposed that bufexamac acts similarly to other non-steroidal anti-inflammatory drugs to inhibit prostaglandin biosynthesis in vitro, via inhibiting cyclo-oxygenase (COX) enzymes 1. Systematically administered bufexamac may accumulate preferentially in the adrenal cortex of rats and may play a role in adrenal stimulation; however its topical anti-inflammatory action is likely to be independent of this effect 1.

TargetActionsOrganism
AProstaglandin G/H synthase 1
inhibitor
Humans
AProstaglandin G/H synthase 2
inhibitor
Humans
UHistone deacetylase 6
inhibitor
Humans
UHistone deacetylase 10
inhibitor
Humans
Absorption

Method of application affects the extent of cutaneous absorption 1. Following rectal administration as suppositories, the systemic absorption was reported to be low 3.

Volume of distribution

No data available.

Protein binding

No data available.

Metabolism

No data available.

Route of elimination

Following topical administration of 5% bufexamac, the recovery in the urine was 3.5% of the applied dose within 144 hours 1. Studies in healthy volunteers receiving an oral dose of 125 to 500 mg indicate that an average of 80% of the total dose is excreted in the urine within 48 hours 1.

Half-life

No data available.

Clearance

No data available.

Adverse Effects
Adverseeffects
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Toxicity

The LD50 in rat following oral and intraperitoneal administration is 3370 mg/kg and 805 mg/kg, respectively MSDS. Subcutaneous LD50 in mouse is >5000 mg/kg MSDS. Mild skin irritation was seen in rabbits following dermal application of 750 mg/30d(l) MSDS. Non-steroidal anti-inflammatory drug (NSAID) overdose may produce nausea, vomiting, indigestion and upper abdominal pain. Other effects may include drowsiness, dizziness, confusion, disorientation, lethargy MSDS.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AceclofenacThe risk or severity of adverse effects can be increased when Aceclofenac is combined with Bufexamac.
AcemetacinThe risk or severity of adverse effects can be increased when Bufexamac is combined with Acemetacin.
Acetylsalicylic acidThe therapeutic efficacy of Acetylsalicylic acid can be decreased when used in combination with Bufexamac.
AlclofenacThe risk or severity of adverse effects can be increased when Alclofenac is combined with Bufexamac.
AminophenazoneThe risk or severity of adverse effects can be increased when Aminophenazone is combined with Bufexamac.
Aminosalicylic acidThe therapeutic efficacy of Aminosalicylic acid can be decreased when used in combination with Bufexamac.
AmitriptylineThe risk or severity of gastrointestinal bleeding can be increased when Amitriptyline is combined with Bufexamac.
AmitriptylinoxideThe risk or severity of gastrointestinal bleeding can be increased when Amitriptylinoxide is combined with Bufexamac.
AmoxapineThe risk or severity of gastrointestinal bleeding can be increased when Amoxapine is combined with Bufexamac.
AntipyrineThe risk or severity of adverse effects can be increased when Antipyrine is combined with Bufexamac.
Interactions
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Food Interactions
No interactions found.

Products

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Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Norfemac Cream - 5%Cream5 %TopicalHoechst Marion Roussel1995-12-311999-08-11Canada flag
Norfemac Ointment - 5%Ointment5 %TopicalHoechst Marion Roussel1995-12-311999-08-11Canada flag

Categories

ATC Codes
M01AB17 — BufexamacM02AA09 — Bufexamac
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as phenylacetamides. These are amide derivatives of phenylacetic acids.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylacetamides
Direct Parent
Phenylacetamides
Alternative Parents
Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Hydroxamic acids / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Alkyl aryl ether / Aromatic homomonocyclic compound / Carbonyl group / Carboxylic acid derivative / Ether / Hydrocarbon derivative / Hydroxamic acid / Organic nitrogen compound / Organic oxide / Organic oxygen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
aromatic ether, hydroxamic acid (CHEBI:31317)
Affected organisms
Not Available

Chemical Identifiers

UNII
4T3C38J78L
CAS number
2438-72-4
InChI Key
MXJWRABVEGLYDG-UHFFFAOYSA-N
InChI
InChI=1S/C12H17NO3/c1-2-3-8-16-11-6-4-10(5-7-11)9-12(14)13-15/h4-7,15H,2-3,8-9H2,1H3,(H,13,14)
IUPAC Name
2-(4-butoxyphenyl)-N-hydroxyacetamide
SMILES
CCCCOC1=CC=C(CC(=O)NO)C=C1

References

General References
  1. Brogden RN, Pinder RM, Sawyer PR, Speight TM, Avery GS: Bufexamac: a review of its pharmacological properties and therapeutic efficacy in inflammatory dermatoses. Drugs. 1975;10(5-6):351-6. [Article]
  2. Kranke B, Szolar-Platzer C, Komericki P, Derhaschnig J, Aberer W: Epidemiological significance of bufexamac as a frequent and relevant contact sensitizer. Contact Dermatitis. 1997 Apr;36(4):212-5. [Article]
  3. Glowania HJ, Hampl B: [Results of a study of the resorption of bufexamac following rectal administration]. Z Hautkr. 1988 Mar 21;63(3):211. [Article]
  4. FDA Thailand: Mastu-S (bufexamac/bismuth subgallate/titanium dioxide/lidocaine hydrochloride) for rectal administration [Link]
KEGG Drug
D01271
PubChem Compound
2466
PubChem Substance
347829293
ChemSpider
2372
BindingDB
50015144
RxNav
1796
ChEBI
31317
ChEMBL
CHEMBL94394
ZINC
ZINC000003871797
PDBe Ligand
A4Z
Wikipedia
Bufexamac
PDB Entries
5bpp
MSDS
Download (352 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CreamTopical
CreamTopical5 %
OintmentTopical5 %
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)153 to 155MSDS
water solubilityImmiscibleMSDS
Predicted Properties
PropertyValueSource
Water Solubility0.233 mg/mLALOGPS
logP2.09ALOGPS
logP1.97ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)8.86ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.56 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity61.29 m3·mol-1ChemAxon
Polarizability24.58 Å3ChemAxon
Number of Rings1ChemAxon
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 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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-1090000000-f24ae0d85b1376dd6695
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00di-5390000000-1064111002b4036cfbbb
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0aor-7900000000-789660a43653a49880b8
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-066r-5900000000-91ae318ee7bf4a0c8ebb
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-4900000000-15c66804db050221c331
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-3900000000-a41498b64629a3eda39c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0920000000-9e2d982e08339f818cf6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0bt9-0900000000-435c1f72113403e534fa
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-9de68224c670d85b5621
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0900000000-496edd1f1dfb18e3bc93
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-1900000000-3e269c82012ba53557c2
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-2900000000-80c7b8b429b26dfbbfc6
MS/MS Spectrum - , positiveLC-MS/MSsplash10-08mi-0920000000-e2854ce6292c5d0a1c8c
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-4910100000-7ff98d442e9aa0a2f64d

Targets

Drugtargets2
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. Brogden RN, Pinder RM, Sawyer PR, Speight TM, Avery GS: Bufexamac: a review of its pharmacological properties and therapeutic efficacy in inflammatory dermatoses. Drugs. 1975;10(5-6):351-6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
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. Brogden RN, Pinder RM, Sawyer PR, Speight TM, Avery GS: Bufexamac: a review of its pharmacological properties and therapeutic efficacy in inflammatory dermatoses. Drugs. 1975;10(5-6):351-6. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an impo...
Gene Name
HDAC6
Uniprot ID
Q9UBN7
Uniprot Name
Histone deacetylase 6
Molecular Weight
131418.19 Da
References
  1. Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dumpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G: Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol. 2011 Mar;29(3):255-65. doi: 10.1038/nbt.1759. Epub 2011 Jan 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes.
Specific Function
Enzyme binding
Gene Name
HDAC10
Uniprot ID
Q969S8
Uniprot Name
Histone deacetylase 10
Molecular Weight
71444.08 Da
References
  1. Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, Bergamini G, Boesche M, Delling M, Dumpelfeld B, Eberhard D, Huthmacher C, Mathieson T, Poeckel D, Reader V, Strunk K, Sweetman G, Kruse U, Neubauer G, Ramsden NG, Drewes G: Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol. 2011 Mar;29(3):255-65. doi: 10.1038/nbt.1759. Epub 2011 Jan 23. [Article]

Drug created on June 23, 2017 20:40 / Updated on May 29, 2021 18:11