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Identification
Name Budesonide
Accession Number DB01222 (APRD00442)
Type small molecule
Groups approved
Description

A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • budesonide
Brand names
  • Bidien
  • Budeson
  • Cortivent
  • Desowen
  • Entocort
  • Entocort EC
  • Micronyl
  • Preferid
  • Pulmicort
  • Pulmicort Nebuamp
  • Pulmicort Respules
  • Pulmicort Turbuhaler
  • Rhinocort
  • Rhinocort Aqua
  • Rhinocort Turbuhaler
  • Spirocort
  • Tridesilon
Brand name mixtures
  • Entocort Enema 0.02 Mg/Ml (Budesonide + Sodium Chloride)
  • Symbicort 100 Turbuhaler (Budesonide + Formoterol Fumarate Dihydrate)
  • Symbicort 200 Turbuhaler (Budesonide + Formoterol Fumarate Dihydrate)
Categories
  • Anti-inflammatory Agents
  • Bronchodilator Agents
  • Corticosteroids
  • Glucocorticoids
CAS number 51333-22-3
Weight Average: 430.5339
Monoisotopic: 430.235538820
Chemical Formula C25H34O6
InChI Key InChIKey=VOVIALXJUBGFJZ-AMTWPJRWSA-N
InChI
InChI=1S/C25H34O6/c1-4-5-21-30-20-11-17-16-7-6-14-10-15(27)8-9-23(14,2)22(16)18(28)12-24(17,3)25(20,31-21)19(29)13-26/h8-10,16-18,20-22,26,28H,4-7,11-13H2,1-3H3/t16-,17-,18-,20+,21-,22+,23-,24-,25+/m0/s1
Plain Text
IUPAC Name
(1S,2S,4R,6S,8S,9S,11S,12S,13R)-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-propyl-5,7-dioxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icosa-14,17-dien-16-one
SMILES
[H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@H](O)C[C@]3(C)[C@@]1(O[C@@H](CCC)O2)C(=O)CO
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Acetals and Derivatives
  • Ethers
  • Dioxoles
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Ketones
Pharmacology
Indication For the treatment of mild to moderate active Crohn's disease. Also for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis.
Pharmacodynamics Budesonide is a synthetic corticosteroid used in Crohn's disease to decrease the symptoms and inflammation associated with the disease, especially at times of flare up. Budesonide has a high topical glucocorticosteroid (GCS) activity and a substantial first pass elimination. The formulation contains granules which are coated to protect dissolution in gastric juice, but which dissolve at pH >5.5, ie, normally when the granules reach the duodenum. Thereafter, a matrix of ethylcellulose with budesonide controls the release of the drug into the intestinal lumen in a time-dependent manner.
Mechanism of action The exact mechanism of action of budesonide in the treatment of Crohn's disease is not fully understood. However, being a glucocorticosteroid, budesonide has a high local anti-inflammatory effect.
Absorption Absorption is complete following oral administration.
Volume of distribution
  • 3 L/kg [asthmatic children 4 to 6 years of age]
Protein binding 85-90%
Metabolism

Following absorption, budesonide is subject to high first pass metabolism (80-90%). In vitro experiments in human liver microsomes demonstrate that budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6b-hydroxy budesonide and 16a- hydroxy prednisolone. The glucocorticoid activity of these metabolites is negligible (<1/100) in relation to that of the parent compound.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 16α-hydroxyprednisolone
Cytochrome P450 3A4 6β-hydroxybudesonide
Route of elimination Budesonide is excreted in urine and feces in the form of metabolites.
Half life 2.0 and 3.6 hours
Clearance
  • 0.5 L/min [Athmatic children 4 to 6 years of age]
Toxicity Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Astrazeneca lp
  • Astrazeneca pharmaceuticals lp
  • Apotex inc
  • Teva parenteral medicines inc
Packagers
Dosage forms
Form Route Strength
Aerosol, metered Nasal
Aerosol, metered Respiratory (inhalation)
Capsule, extended release Oral
Suspension Nasal
Suspension Respiratory (inhalation)
Prices
Unit description Cost Unit
Budesonide micronized powder 346.5 USD g
DesOwen Lot w/Cetaphil Cream 0.05% Kit Box 255.84 USD box
Desowen 0.05% ointment kit 217.2 USD kit
Desowen 0.05% cream kit 212.4 USD kit
DesOwen 0.05% Lotion 118ml Bottle 183.17 USD bottle
Pulmicort Flexhaler 180 mcg/act Aerosol Inhaler 163.34 USD inhaler
Pulmicort 180 mcg flexhaler 157.06 USD inhaler
DesOwen 0.05% Lotion 59ml Bottle 123.38 USD bottle
Pulmicort Flexhaler 90 mcg/act Aerosol Inhaler 121.98 USD inhaler
Pulmicort 90 mcg flexhaler 117.29 USD inhaler
Rhinocort Aqua 32 mcg/act 8.6 gm Bottle 111.96 USD bottle
Rhinocort aqua nasal spray 13.93 USD g
Entocort EC 3 mg 24 Hour Capsule 13.86 USD capsule
Entocort ec 3 mg capsule 12.22 USD capsule
Budesonide 0.5 mg/2ml Suspension 2ml Plastic Container 9.73 USD plastic
Pulmicort 0.5 mg/2ml Suspension 2ml Plastic Container 9.24 USD plastic
Budesonide 0.25 mg/2ml Suspension 2ml Plastic Container 9.07 USD plastic
Entocort (115 Ml) 2.3 mg/enm Enema 8.93 USD enema
Pulmicort 1 mg/2 ml respule 8.89 USD ml
Pulmicort 0.25 mg/2ml Suspension 2ml Plastic Container 7.85 USD plastic
Pulmicort 0.5 mg/2 ml respule 4.45 USD ml
Pulmicort 0.25 mg/2 ml respul 3.78 USD ml
Desowen 0.05% cream 2.43 USD g
Pulmicort Nebuamp 0.5 mg/ml Suspension 0.93 USD ml
Pulmicort Turbuhaler 400 mcg/dose Metered Inhalation Powder 0.62 USD dose
Pulmicort Nebuamp 0.25 mg/ml Suspension 0.46 USD ml
Pulmicort Turbuhaler 200 mcg/dose Metered Inhalation Powder 0.34 USD dose
Pulmicort Nebuamp 0.125 mg/ml Suspension 0.23 USD ml
Pulmicort Turbuhaler 100 mcg/dose Metered Inhalation Powder 0.17 USD dose
Rhinocort Turbuhaler 100 mcg/dose Metered Dose Aerosol 0.13 USD dose
Mylan-Budesonide Aq 100 mcg/dose Metered Dose Spray 0.1 USD dose
Patents
Country Patent Number Approved Expires
United States 6598603 1999-06-23 2019-06-23
United States 6423340 1993-11-15 2010-11-15
Canada 2071518 2002-11-12 2010-11-15
Properties
State solid
Melting point 221-232 oC
Experimental Properties
Property Value Source
water solubility insoluble PhysProp
logP 1.9 PhysProp
Predicted Properties
Property Value Source
water solubility 4.57e-02 g/l ALOGPS
logP 2.42 ALOGPS
logP 2.73 ChemAxon Molconvert
logS -3.97 ALOGPS
pKa 14.91 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 93.06 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 116.11 ChemAxon Molconvert
polarizability 47.11 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00246 Link_out
PubChem Compound 63006 Link_out
PubChem Substance 46504869 Link_out
ChemSpider 56704 Link_out
ChEBI 3207 Link_out
ChEMBL 3207 Link_out
Therapeutic Targets Database DAP000320 Link_out
PharmGKB PA448681 Link_out
Drug Product Database 2241003 Link_out
RxList http://www.rxlist.com/cgi/generic/entocort.htm Link_out
Drugs.com http://www.drugs.com/cdi/budesonide-spray.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/cx1621.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Budesonide Link_out
ATC Codes
  • A07EA06
  • D07AC09
  • R01AD05
  • R03BA02
AHFS Codes
  • 52:08.08
  • 68:04.00
PDB Entries Not Available
FDA label show (52.3 KB)
MSDS show (73.7 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • A mean delay in time to peak concentration of 2.5 hours is observed with the intake of a high-fat meal, with no significant differences in AUC.
Targets

1. Glucocorticoid receptor

Pharmacological action: yes
Actions: antagonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhang X, Moilanen E, Kankaanranta H: Enhancement of human eosinophil apoptosis by fluticasone propionate, budesonide, and beclomethasone. Eur J Pharmacol. 2000 Oct 20;406(3):325-32. Pubmed
  2. Henriksson G, Norlander T, Forsgren J, Stierna P: Effects of topical budesonide treatment on glucocorticoid receptor mRNA down-regulation and cytokine patterns in nasal polyps. Am J Rhinol. 2001 Jan-Feb;15(1):1-8. Pubmed
  3. Zhang X, Moilanen E, Kankaanranta H: Beclomethasone, budesonide and fluticasone propionate inhibit human neutrophil apoptosis. Eur J Pharmacol. 2001 Nov 23;431(3):365-71. Pubmed
  4. Kompella UB, Bandi N, Ayalasomayajula SP: Subconjunctival nano- and microparticles sustain retinal delivery of budesonide, a corticosteroid capable of inhibiting VEGF expression. Invest Ophthalmol Vis Sci. 2003 Mar;44(3):1192-201. Pubmed
  5. Kunz S, Sandoval R, Carlsson P, Carlstedt-Duke J, Bloom JW, Miesfeld RL: Identification of a novel glucocorticoid receptor mutation in budesonide-resistant human bronchial epithelial cells. Mol Endocrinol. 2003 Dec;17(12):2566-82. Epub 2003 Aug 14. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Jonsson G, Astrom A, Andersson P: Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug Metab Dispos. 1995 Jan;23(1):137-42. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 28, 2011 13:44

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.