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Identification
NameBeclomethasone
Accession NumberDB00394  (APRD00564)
Typesmall molecule
Groupsapproved, investigational
Description

Beclomethasone dipropionate is a prodrug of the free form, Beclomethasone (beclomethasone-17-monopropionate). An anti-inflammatory, synthetic corticosteroid, it is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma and allergic rhinitis (seasonal and perennial). Beclometasone dipropionate is also being investigated for oral treatment in mild-to-moderate Crohn’s disease of ileal or ileal-right colonic localisation and for “topical” use mild-to-moderate graft versus host disease. It is marketed under several brand names such as Qnasl (US) and Rivanase AQ (Canada).

Structure
Thumb
Synonyms
SynonymLanguageCode
(11beta,16beta)-9-chloro-11-Hydroxy-16-methyl-17,21-bis(1-oxopropoxy)pregna-1,4-diene-3,20-dioneNot AvailableNot Available
9-chloro-11beta-Hydroxy-16beta-methylpregna-1,4-diene-3,20-dione 17,21-dipropionateNot AvailableNot Available
9-chloro-11β,17,21-trihydroxy-16β-methylpregna-1,4-diene-3,20-dioneNot AvailableNot Available
9-chloro-16beta-Methyl-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 17,21-dipropionateNot AvailableNot Available
9α-chloro-16β-methylprednisoloneNot AvailableNot Available
AerobecNot AvailableNot Available
AldecinNot AvailableNot Available
AnceronNot AvailableNot Available
AndionNot AvailableNot Available
BeclacinNot AvailableNot Available
BecloforteNot AvailableNot Available
BeclometNot AvailableNot Available
BeclometasoneNot AvailableNot Available
Beclometasone 17,21-dipropionateNot AvailableNot Available
Beclometasone dipropionateNot AvailableNot Available
Beclomethasone dipropionateNot AvailableNot Available
BeclorhinolNot AvailableNot Available
BeclovalNot AvailableNot Available
BecloventNot AvailableNot Available
BecodisksNot AvailableNot Available
BeconaseNot AvailableNot Available
BeconasolNot AvailableNot Available
BecotideNot AvailableNot Available
Clenil-aNot AvailableNot Available
EntydermaNot AvailableNot Available
InaloneNot AvailableNot Available
KorbutoneNot AvailableNot Available
PropadermNot AvailableNot Available
Rino-clenilNot AvailableNot Available
SanasthmaxNot AvailableNot Available
SanasthmylNot AvailableNot Available
VancenaseNot AvailableNot Available
VancerilNot AvailableNot Available
ViarexNot AvailableNot Available
ViaroxNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AerobecTeva
AldecinSchering-Plough
AnceronNot Available
AndionNot Available
BeclacinMayado Seiyaku
BecloforteGlaxoSmithKline
BeclometOrion
BeclorhinolChiesi
BeclovalNot Available
BecloventGlaxoSmithKline
BecodisksGlaxoSmithKline
BeconaseGlaxoSmithKline
BeconasolNot Available
BecotideGlaxoSmithKline
Clenil-ANot Available
EntydermaNot Available
InaloneGlaxoSmithKline
KorbutoneNot Available
orBecDOR BioPharma, Inc.
PropadermGlaxoSmithKline
Qnasl Teva Pharmaceuticals
QVARTeva Respiratory
Rino-ClenilChiesi
RivanaseNot Available
SanasthmaxChiesi
SanasthmylNot Available
VancenaseNot Available
VancerilNot Available
Brand mixturesNot Available
Categories
CAS number5534-09-8
WeightAverage: 521.042
Monoisotopic: 520.222781245
Chemical FormulaC28H37ClO7
InChI KeyKUVIULQEHSCUHY-XYWKZLDCSA-N
InChI
InChI=1S/C28H37ClO7/c1-6-23(33)35-15-22(32)28(36-24(34)7-2)16(3)12-20-19-9-8-17-13-18(30)10-11-25(17,4)27(19,29)21(31)14-26(20,28)5/h10-11,13,16,19-21,31H,6-9,12,14-15H2,1-5H3/t16-,19-,20-,21-,25-,26-,27-,28-/m0/s1
IUPAC Name
2-[(1R,2S,10S,11S,13S,14R,15S,17S)-1-chloro-17-hydroxy-2,13,15-trimethyl-5-oxo-14-(propanoyloxy)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-3,6-dien-14-yl]-2-oxoethyl propanoate
SMILES
[H][C@@]12C[C@H](C)[C@](OC(=O)CC)(C(=O)COC(=O)CC)[C@@]1(C)C[C@H](O)[C@@]1(Cl)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C
Mass Specshow(11.1 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassGluco/mineralocorticoids, Progestogins and Derivatives
Direct parentGluco/mineralocorticoids, Progestogins and Derivatives
Alternative parentsSteroid Esters; Halogenated Steroids; Hydroxysteroids; Ketosteroids; Iridoids and Derivatives; Cyclohexanols; Dicarboxylic Acids and Derivatives; Carboxylic Acid Esters; Cyclic Alcohols and Derivatives; Chlorohydrins; Ketones; Ethers; Enolates; Polyamines; Organochlorides; Alkyl Chlorides; Aldehydes
Substituents3-keto-steroid; 11-hydroxy-steroid; 9-halo-steroid; 20-keto-steroid; 11-noriridane monoterpene; monoterpene; cyclohexanol; dicarboxylic acid derivative; cyclic alcohol; chlorohydrin; halohydrin; carboxylic acid ester; ketone; secondary alcohol; polyamine; enolate; ether; carboxylic acid derivative; alcohol; organohalogen; organochloride; carbonyl group; alkyl halide; alkyl chloride; aldehyde
Classification descriptionThis compound belongs to the gluco/mineralocorticoids, progestogins and derivatives. These are steroids whose structure is based on an hydroxylated prostane moiety.
Pharmacology
IndicationUsed in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older, and in treating symptoms for allergic rhinitis (seasonal or perennial) in patients 12 years of age and older. Also being investigated for oral treatment in mild-to-moderate Crohn's disease of ileal or ileal-right colonic localisation and for "topical" use mild-to-moderate graft versus host disease.
PharmacodynamicsBeclometasone, a synthetic halogenated glucocorticoid with antiinflammatory and vasoconstrictive effects, is used for treating steroid-dependent asthma, allergic or nonallergic rhinitis, or recurrent nasal polyps.
Mechanism of actionUnbound corticosteroids cross cell membranes and bind with high affinity to specific cytoplasmic receptors. The result includes inhibition of leukocyte infiltration at the site of inflammation, interference in the function of mediators of inflammatory response, suppression of humoral immune responses, and reduction in edema or scar tissue. The antiinflammatory actions of corticosteroids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. For the investigated use in the treatment of GvHD or Crohn's, beclometasone acts by binding to interleukin-13 to inhibit cytokines, which in turn inhibits inflammatory chemicals downstream.
AbsorptionMean peak plasma concentration was 88pg/ml at 0.5 hour
Volume of distribution

The steady state volume of distribution for beclomethasone dipropionate is 20 L, and for it’s active metabolite, beclomethasone-17-monopropionate, it is much larger at 424 L.

Protein binding87% to albumin and transcortin
Metabolism

Metabolism mediated via esterase enzymes that are found in most tissues. Undergoes rapid and extensive conversion to beclomenthasone-17-monopropionate (17-BMP) during absorption

Route of eliminationIrrespective of the route of administration (injection, oral or inhalation), BDP and its metabolites are mainly excreted in the feces. Less than 10% of the drug and its metabolites are excreted in the urine.
Half life2.8 hours
Clearance

High plasma clearance after intravenous administration (150 and 120 L/hour).

ToxicityThe acute toxicity of beclometasone dipropionate is low. The only harmful effect that follows inhalation of large amounts of the drug over a short period of time is suppression of hypothalamic-pituitary-adrenal (HPA) function. Chronic: The excessive use of beclometasone dipropionate over a long period could lead to adrenal suppression.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9904
Blood Brain Barrier + 0.9851
Caco-2 permeable + 0.5698
P-glycoprotein substrate Substrate 0.7529
P-glycoprotein inhibitor I Inhibitor 0.5986
P-glycoprotein inhibitor II Non-inhibitor 0.7488
Renal organic cation transporter Non-inhibitor 0.7907
CYP450 2C9 substrate Non-substrate 0.8634
CYP450 2D6 substrate Non-substrate 0.9174
CYP450 3A4 substrate Substrate 0.784
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.7516
CYP450 2C19 substrate Non-inhibitor 0.9122
CYP450 3A4 substrate Non-inhibitor 0.7875
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8577
Ames test Non AMES toxic 0.938
Carcinogenicity Non-carcinogens 0.914
Biodegradation Not ready biodegradable 0.9932
Rat acute toxicity 2.1115 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9456
hERG inhibition (predictor II) Non-inhibitor 0.6054
Pharmacoeconomics
Manufacturers
  • Glaxosmithkline
  • Schering corp sub schering plough corp
  • Schering corp
Packagers
Dosage forms
FormRouteStrength
Aerosol, meteredNasal
Aerosol, meteredNasal0.08MG/ACTUATION
Aerosol, meteredRespiratory (inhalation)
CreamTopical
SprayNasal
SuspensionNasal
Prices
Unit descriptionCostUnit
Beconase AQ 42 mcg/spray Suspension 25 gm Inhaler149.32USDinhaler
Beclomethasone dipro powder107.1USDg
Qvar 80 mcg/act Aerosol 7.3 gm Inhaler105.64USDinhaler
Qvar 40 mcg/act Aerosol 7.3 gm Inhaler87.5USDinhaler
Qvar 80 mcg inhaler19.05USDg
Qvar 40 mcg inhaler15.12USDg
Propaderm 250 mcg/g Cream0.46USDg
Qvar Cfc-Free 100 mcg/dose Metered Dose Aerosol0.33USDdose
Qvar Cfc-Free 50 mcg/dose Metered Dose Aerosol0.16USDdose
Apo-Beclomethasone 50 mcg/dose Metered Dose Spray0.06USDdose
Mylan-Beclo Aq. 50 mcg/dose Metered Dose Spray0.06USDdose
Nu-Beclomethasone 50 mcg/dose Metered Dose Spray0.06USDdose
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point117-120 °CNot Available
water solubility49.39 mg/LNot Available
logP1.3Not Available
Predicted Properties
PropertyValueSource
water solubility2.08e-03 g/lALOGPS
logP3.69ALOGPS
logP4.43ChemAxon
logS-5.4ALOGPS
pKa (strongest acidic)13.85ChemAxon
pKa (strongest basic)-3.3ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count1ChemAxon
polar surface area106.97ChemAxon
rotatable bond count8ChemAxon
refractivity134.79ChemAxon
polarizability54.41ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Taub, D., Wendler, N.L. and Slates, H.L.; US.Patent 3,345,387; October 3, 1967; assigned
to Merck & Co., Inc.

General Reference
  1. Willey RF, Milne LJ, Crompton GK, Grant IW: Beclomethasone dipropionate aerosol and oropharyngeal candidiasis. Br J Dis Chest. 1976 Jan;70(1):32-8. Pubmed
  2. Salzman GA, Pyszczynski DR: Oropharyngeal candidiasis in patients treated with beclomethasone dipropionate delivered by metered-dose inhaler alone and with Aerochamber. J Allergy Clin Immunol. 1988 Feb;81(2):424-8. Pubmed
  3. Fukushima C, Matsuse H, Tomari S, Obase Y, Miyazaki Y, Shimoda T, Kohno S: Oral candidiasis associated with inhaled corticosteroid use: comparison of fluticasone and beclomethasone. Ann Allergy Asthma Immunol. 2003 Jun;90(6):646-51. Pubmed
  4. Astegiano M, Pagano N, Sapone N, Simondi D, Bertolusso L, Bresso F, Demarchi B, Pellicano R, Bonardi R, Marconi S, Rizzetto M: Efficacy and safety of oral beclomethasone dipropionate for ileal or ileal-right colon Crohn’s disease of mild-to-moderate activity or in remission: Retrospective study. Biomed Pharmacother. 2007 Jul;61(6):370-6. Epub 2007 Mar 12. Pubmed
  5. McDonald GB: Oral beclomethasone dipropionate: a topically active corticosteroid for the treatment of gastrointestinal graft-versus-host disease following allogeneic hematopoietic cell transplantation. Expert Opin Investig Drugs. 2007 Oct;16(10):1709-24. Pubmed
  6. Hockenbery DM, Cruickshank S, Rodell TC, Gooley T, Schuening F, Rowley S, David D, Brunvand M, Berryman B, Abhyankar S, Bouvier M, McDonald GB: A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease. Blood. 2007 May 15;109(10):4557-63. Epub 2007 Jan 23. Pubmed
  7. Castilla C, Perez-Simon JA, Sanchez-Guijo FM, Diez-Campelo M, Ocio E, Perez-Persona E, Lopez-Villar O, Vazquez L, Caballero D, San Miguel JF: Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD). Biol Blood Marrow Transplant. 2006 Sep;12(9):936-41. Pubmed
  8. FDA label.
External Links
ResourceLink
KEGG DrugD07495
KEGG CompoundC06842
ChEBI3001
ChEMBLCHEMBL1200500
Therapeutic Targets DatabaseDAP000416
PharmGKBPA448547
Drug Product Database2238796
RxListhttp://www.rxlist.com/qvar-drug.htm
Drugs.comhttp://www.drugs.com/cdi/beclomethasone-spray.html
WikipediaBeclometasone_dipropionate
ATC CodesA07EA07D07AC15R01AD01R03BA01
AHFS Codes
  • 52:08.08
  • 84:06.00
  • 68:04.00
PDB EntriesNot Available
FDA labelshow(255 KB)
MSDSshow(73.6 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Glucocorticoid receptor

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Glucocorticoid receptor P04150 Details

References:

  1. Saklatvala J: Glucocorticoids: do we know how they work? Arthritis Res. 2002;4(3):146-50. Epub 2002 Jan 21. Pubmed
  2. Issar M, Sahasranaman S, Buchwald P, Hochhaus G: Differences in the glucocorticoid to progesterone receptor selectivity of inhaled glucocorticoids. Eur Respir J. 2006 Mar;27(3):511-6. Pubmed
  3. Usmani OS, Ito K, Maneechotesuwan K, Ito M, Johnson M, Barnes PJ, Adcock IM: Glucocorticoid receptor nuclear translocation in airway cells after inhaled combination therapy. Am J Respir Crit Care Med. 2005 Sep 15;172(6):704-12. Epub 2005 Apr 28. Pubmed

Enzymes

1. Cytochrome P450 3A5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Cytochrome P450 3A5 P20815 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Corticosteroid-binding globulin

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: binder

Components

Name UniProt ID Details
Corticosteroid-binding globulin P08185 Details

References:

  1. Landyshev IuS, Grigorenko AA, Marikhina NS, Molochnaia SV: [A comparative assessment of the effect of different methods of glucocorticosteroid therapy on the hypophyseal-adrenal system in bronchial asthma patients] Ter Arkh. 1995;67(3):43-7. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Comments
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Drug created on June 13, 2005 07:24 / Updated on March 31, 2014 13:28