NAV

Betamethasone phosphate

Identification

Summary

Betamethasone phosphate is a fast acting ester prodrug of a corticosteroid used to treat inflammatory conditions.

Generic Name
Betamethasone phosphate
DrugBank Accession Number
DB14669
Background

Betamethasone phosphate is a prodrug that is rapidly hydrolyzed, providing rapidly accessible betamethasone to agonize glucocorticoid receptors.5 Betamethasone provides greater anti-inflammatory activity than prednisolone with less sodium and water retention.5

Betamethasone sodium phosphate was granted FDA approval on 3 March 1965.5

Type
Small Molecule
Groups
Approved, Vet approved
Structure
3D
Similar Structures
Weight
Average: 472.446
Monoisotopic: 472.166233087
Chemical Formula
C22H30FO8P
Synonyms
  • Betamethasone 21-(dihydrogen phosphate)
  • Betamethasone 21-phosphate
  • Betamethasone dihydrogen phosphate
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Pharmacology

Indication

Betamethasone phosphate is indicated intramuscularly to treat allergic states, dermatologic diseases, endocrine disorders, gastrointestinal diseases, hematologic disorders, neoplastic diseases, nervous system conditions, ophthalmic diseases, renal diseases, respiratory diseases, rheumatic disorders, trichinosis with neurologic or myocardial involvement, and tuberculous meningitis with subarachnoid block or impending block.5 It is also used intra-articularly in the treatment of acute gouty arthritis, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, and synovitis of osteoarthritis.5 Intralesional betamethasone phospahte is indicated in the treatment of alopecia areata, discoid lupus erythematosus, keloids, lichen planus, lichen simplex chronicus, psoriatic plaques, necrobiosis lipoidica diabeticorum, and localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare.5

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofAcute gouty arthritis•••••••••••••••••••••
Treatment ofAllergic conditions•••••••••••••••••••••
Treatment ofAlopecia areata (aa)•••••••••••••••••••••
Treatment ofDermatological disease•••••••••••••••••••••
Treatment ofDiscoid lupus erythematosus (dle)•••••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals.2 Betamethasone phosphate has a short duration of action as it is rapidly hydrolyzed to betamethasone.5 Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces.2 Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.2

Mechanism of action

Betamethasone phosphate is a soluble ester prodrug of betamethasone.5 Betamethasone is rapidly de-esterified, allowing betamethasone to act as an agonist of the glucocorticoid receptor.5 The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation.2 Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.2

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.2

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.2 High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.2

TargetActionsOrganism
UGlucocorticoid receptor
agonist
Humans
UAnnexin A1
agonist
Humans
Absorption

An intramuscular injection of 3mg betamethasone acetate and 3mg betametasone phosphate reaches a betamethasone Cmax 33.21 ± 8.71 ng/mL, with a Tmax of 1.56 ± 1.32 h, and an AUC of 506.95 ± 125.03 ng*h/mL.1

Volume of distribution

The volume of distribution of betamethasone in an intramuscular injection of 3mg betamethasone acetate and 3mg betamethasone phosphate is 226.00 ± 61.64 L.1

Protein binding

Corticosteroids are generally bound to corticosteroid binding globulin3 and serum albumin4 in plasma.

Metabolism

Betamethasone phosphate is rapidly de-esterified to betamethasone.5

Hover over products below to view reaction partners

Route of elimination

Corticosteroids are eliminated predominantly in the urine.4

Half-life

The half life of betamethasone in an intramuscular injection of 3mg betamethasone acetate and 3mg betamethasone phosphate is 12.47 ± 1.91 h.1

Clearance

The clearance of betamethasone in an intramuscular injection of 3mg betamethasone acetate and 3mg betamethasone phosphate is 12.62 ± 3.45 L/h.1

Adverse Effects
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Toxicity

Patients experiencing an acute overdose should be treated with symptomatic and supportive treatment.5 Chronic overdoses where patients require continued therapy can be treated through temporary dose reduction or alternate day treatment.5

The oral, intraperitoneal, and intravenous LD50 values in rats are 1877 mg/kg, 1179 mg/kg, and 1276 mg/kg, respectively.6

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.
DrugInteraction
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interactions in your software
AbametapirThe serum concentration of Betamethasone phosphate can be increased when it is combined with Abametapir.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Betamethasone phosphate.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Betamethasone phosphate.
AcarboseThe risk or severity of hyperglycemia can be increased when Betamethasone phosphate is combined with Acarbose.
AceclofenacThe risk or severity of gastrointestinal irritation can be increased when Betamethasone phosphate is combined with Aceclofenac.
Food Interactions
No interactions found.

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 11-beta-hydroxysteroids / 17-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Glycerone phosphates / Monoalkyl phosphates / Tertiary alcohols / Alpha-hydroxy ketones
show 8 more
Substituents
11-beta-hydroxysteroid / 11-hydroxysteroid / 17-hydroxysteroid / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 9-halo-steroid / Alcohol / Aliphatic homopolycyclic compound / Alkyl fluoride
show 26 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
11beta-hydroxy steroid, 17alpha-hydroxy steroid, 20-oxo steroid, steroid phosphate, fluorinated steroid, 3-oxo-Delta(1),Delta(4)-steroid (CHEBI:68603)
Affected organisms
Not Available

Chemical Identifiers

UNII
YJO1F9W10R
CAS number
360-63-4
InChI Key
VQODGRNSFPNSQE-DVTGEIKXSA-N
InChI
InChI=1S/C22H30FO8P/c1-12-8-16-15-5-4-13-9-14(24)6-7-19(13,2)21(15,23)17(25)10-20(16,3)22(12,27)18(26)11-31-32(28,29)30/h6-7,9,12,15-17,25,27H,4-5,8,10-11H2,1-3H3,(H2,28,29,30)/t12-,15-,16-,17-,19-,20-,21-,22-/m0/s1
IUPAC Name
{2-[(1R,2S,3aS,3bS,9aS,9bR,10S,11aS)-9b-fluoro-1,10-dihydroxy-2,9a,11a-trimethyl-7-oxo-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-yl]-2-oxoethoxy}phosphonic acid
SMILES
[H][C@@]12C[C@H](C)[C@](O)(C(=O)COP(O)(O)=O)[C@@]1(C)C[C@H](O)[C@@]1(F)[C@@]2([H])CCC2=CC(=O)C=C[C@]12C

References

General References
  1. Salem II, Najib NM: Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects. Clin Ther. 2012 Jan;34(1):214-20. doi: 10.1016/j.clinthera.2011.11.022. Epub 2011 Dec 9. [Article]
  2. Yasir M, Sonthalia S: Corticosteroid Adverse Effects . [Article]
  3. Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA: Corticosteroid-binding globulin: structure-function implications from species differences. PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. [Article]
  4. Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003. [Article]
  5. FDA Approved Drug Products: Celestone Soluspan (betamethasone sodium phosphate and betamethasone acetate) injectable suspension [Link]
  6. British Pharmacopoeia: Betamethasone Sodium Phosphate MSDS [Link]
ChemSpider
96937
ChEBI
68603
ChEMBL
CHEMBL1201207
ZINC
ZINC000004097469
Wikipedia
Betamethasone_phosphate

Clinical Trials

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PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.9 mg/mLALOGPS
logP1.21ALOGPS
logP1.56Chemaxon
logS-2.2ALOGPS
pKa (Strongest Acidic)1.18Chemaxon
pKa (Strongest Basic)-3.4Chemaxon
Physiological Charge-2Chemaxon
Hydrogen Acceptor Count7Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area141.36 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity113.37 m3·mol-1Chemaxon
Polarizability45.43 Å3Chemaxon
Number of Rings4Chemaxon
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/MSsplash10-0a4r-0005900000-f0092597cf9efcd2f584
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-2000900000-11c9627c0b5cdb9f560c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1419700000-d40877694a6f2e42299a
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9000200000-4a1fb22b468d90d0f72e
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9004000000-5437f957337f3350fb88
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-02ti-0594100000-9dd6165d0859be483548
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-195.75475
predicted
DeepCCS 1.0 (2019)
[M+H]+197.65013
predicted
DeepCCS 1.0 (2019)
[M+Na]+203.47047
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Details1. Glucocorticoid receptor
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003. [Article]
Details2. Annexin A1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Structural molecule activity
Specific Function
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity (PubMed:8425544). Play...
Gene Name
ANXA1
Uniprot ID
P04083
Uniprot Name
Annexin A1
Molecular Weight
38713.855 Da
References
  1. Serres M, Viac J, Comera C, Schmitt D: Expression of annexin I in freshly isolated human epidermal cells and in cultured keratinocytes. Arch Dermatol Res. 1994;286(5):268-72. [Article]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]
  2. FDA Approved Drug Products: Celestone Soluspan (betamethasone sodium phosphate and betamethasone acetate) injectable suspension [Link]
Details2. Cytochrome P450 3A5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Dvorak Z, Pavek P: Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids. Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462. [Article]

Carriers

Details1. Corticosteroid-binding globulin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Gardill BR, Vogl MR, Lin HY, Hammond GL, Muller YA: Corticosteroid-binding globulin: structure-function implications from species differences. PLoS One. 2012;7(12):e52759. doi: 10.1371/journal.pone.0052759. Epub 2012 Dec 26. [Article]
Details2. Serum albumin
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Czock D, Keller F, Rasche FM, Haussler U: Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003. [Article]

Transporters

Details1. Solute carrier organic anion transporter family member 1A2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Bossuyt X, Muller M, Hagenbuch B, Meier PJ: Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J Pharmacol Exp Ther. 1996 Mar;276(3):891-6. [Article]
Details2. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Yates CR, Chang C, Kearbey JD, Yasuda K, Schuetz EG, Miller DD, Dalton JT, Swaan PW: Structural determinants of P-glycoprotein-mediated transport of glucocorticoids. Pharm Res. 2003 Nov;20(11):1794-803. [Article]
  2. Matoulkova P, Pavek P, Maly J, Vlcek J: Cytochrome P450 enzyme regulation by glucocorticoids and consequences in terms of drug interaction. Expert Opin Drug Metab Toxicol. 2014 Mar;10(3):425-35. doi: 10.1517/17425255.2014.878703. Epub 2014 Jan 23. [Article]
Details3. Solute carrier family 22 member 8
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [Article]

Drug created at September 03, 2018 17:11 / Updated at July 01, 2020 02:41