Beclomethasone dipropionate

Identification

Summary

Beclomethasone dipropionate is an inhaled corticosteroid used as maintenance treatment in the prophylaxis of asthma attacks.

Brand Names
Alanase, Beconase, Propaderm, Qnasl, Qvar, Rivanase AQ
Generic Name
Beclomethasone dipropionate
DrugBank Accession Number
DB00394
Background

Beclomethasone dipropionate is a second-generation10 synthetic corticosteroid and diester of beclomethasone, which is structurally similar to dexamethasone.11 It is a prodrug of an active metabolite beclomethasone 17-monopropionate (17-BMP)1 which acts on the glucocorticoid receptor to mediates its therapeutic action. Beclomethasone dipropionate itself posesses weak glucocorticoid receptor binding affinity and is rapidly converted into 17-BMP upon administration.1 Formulations for oral inhalation, intranasal, and topical use are available for beclomethasone dipropionate. Beclomethasone dipropionate became first available in a pressurized metered-dose inhaler in 1972 and later in a dry powder inhaler and an aqueous nasal spray.1 Due to its anti-inflammatory, antipruritic, and anti-allergy properties, beclomethasone dipropionate is used in various inflammatory conditions, such as asthma, allergic rhinitis, and dermatoses to reduce symptoms. When inhaled, it is proposed that beclomethasone dipropionate remains active locally in the lung without causing significant side effects associated with systemic corticosteroids.8 Compared to earlier corticosteroids such as dexamethasone and prednisolone, beclomethasone dipropionate is reported to be less irritating to the nasal mucosa with a longer duration of action when administered intranasally.3

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 521.042
Monoisotopic: 520.222781245
Chemical Formula
C28H37ClO7
Synonyms
  • (11β,16β)-9-chloro-11-hydroxy-16-methyl-17,21-bis(1-oxopropoxy)pregna-1,4-diene-3,20-dione
  • 9-chloro-11β-hydroxy-16β-methylpregna-1,4-diene-3,20-dione 17,21-dipropionate
  • 9-chloro-16β-methyl-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 17,21-dipropionate
  • beclometasone 17,21-dipropionate
  • Beclometasone dipropionate
  • Beclometasone dipropionate anhydrous
  • Beclometasone dipropionato
  • Beclomethasone dipropionate
External IDs
  • SCH 18020W
  • SCH 8020W
  • SCH-18020W
  • SGX-201
  • SGX-202
  • SGX-203

Pharmacology

Indication

Indicated for oral inhalation use in the maintenance treatment of asthma as prophylactic therapy in patients 5 years of age and older. The aerosol form of beclomethasone diproprionate is not indicated for the relief of acute bronchospasm.11

Indicated for intranasal use to relieve the symptoms of seasonal or perennial allergic and nonallergic (vasomotor) rhinitis and prevent the recurrence of nasal polyps following surgical removal.12

Indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age and older.14 Corticosteroid-responsive dermatoses include psoriasis, contact dermatitis (dermatitis venenata), atopic dermatitis (infantile eczema, allergic dermatitis), neurodermatitis (lichen simplex chronicus, lichen planus, eczema, eczematous dermatitis), intertrigo, dyshidroses (pompholyx), seborrheic dermatitis, exfoliative dermatitis, solar dermatitis, stasis dermatitis, and anogenital and senile pruritus.13

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Adjunct therapy in treatment ofAcute bacterial rhinosinusitis••• ••••••••••
Used as adjunct in combination to manageAsthmaCombination Product in combination with: Salbutamol (DB01001)•••••••••••••••••••
Management ofAsthma••••••••••••••••••••
Symptomatic treatment ofChronic rhinosinusitis••• ••••••••••
Symptomatic treatment ofDermatosis••••••••••••••••••••••• ••••••••••••••••••••••••••••••••••••• ••••••••
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Inflammatory conditions, including asthma, dermatoses, and allergic rhinitis, involve the activation of cascades by inflammatory mediators. Inflammation is a primary defense mechanism and the homeostatic response of the immune system; however, a prolonged inflammatory response in certain disorders may lead to tissue damage, pain, and swelling. Beclomethasone dipropionate works by attenuating the inflammatory responses associated with asthma, allergic rhinitis, nasal polyps, and corticosteroid-responsive dermatoses. It suppresses the actions of inflammatory cells, such as mast cells, eosinophils, basophils, lymphocytes, macrophages, and neutrophils. It also inhibits the release of inflammatory mediators, such as histamine, eicosanoids, leukotrienes, and cytokines.11 Beclomethasone dipropionate is reported to exhibit potent topical activity while possessing low systemic effects.2

Beclomethasone dipropionate is a corticosteroid drug with anti-inflammatory and vasoconstrictive effects used to treat chronic inflammatory processes such as asthma, allergic rhinitis, corticosteroid-responsive dermatoses. When inhaled, it improves lung function, decreases airway hyper-reactivity, and reduces the severity of asthmatic symptoms.9 Although inhaled corticosteroids, including beclomethasone dipropionate, are reported to mainly act locally in the lungs, systemic effects such as disruption of hypothalamic-pituitary-adrenal (HPA) axis function, bone turnover, osteoporosis, and growth suppression may still be observed with chronic use or high dose administration. There were varying findings from clinical studies examining the effect of beclomethasone dipropionate on growth suppression in pediatric patients.9 It was shown to suppress the hypothalamo-pituitary-adrenal (HPA) axis in a dose-dependent manner.6 HPA axis is a central hormonal response system to stress and activation of HPA axis leads to the production of endogenous steroid hormone production.7 Long-term use of high-dose systemic corticosteroids, including those inhaled, was often associated with signs and symptoms of adrenal insufficiency when exposed to stress conditions, such as trauma, surgery, or infections. As corticosteroids work by suppressing the immune system, there may be an increased risk for developing infections.11 Cases of Candida albicans infection of the mouth and throat have been reported with inhaled beclomethasone dipropionate therapy.8

Mechanism of action

Beclomethasone dipropionate is a corticosteroid and prodrug that is rapidly activated by hydrolysis to the active monoester, 17 monopropionate (17-BMP), which mediates anti-inflammatory actions. 17-BMP has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor which is approximately 13 times that of dexamethasone and 25 times that of beclomethasone dipropionate.11 Upon binding of the ligand, the glucocorticoid receptors dimerize and translocate into the nucleus, where they subsequently bind to glucocorticoid response elements (GRE) on glucocorticoid-responsive genes, leading to changes in transcription. There are several proposed mechanisms for the anti-inflammatory action of corticosteroids. Corticosteroids may work by increasing the transcription of genes coding for anti-inflammatory proteins, including lipocortin-1 and interleukin-10.4 Corticosteroids were also shown to inhibit the expression of multiple genes that encode pro-inflammatory factors, such as cytokines, chemokines, and adhesion molecules, that are activated during the chronic inflammatory process.5 This is thought to be due to the direct inhibitory interaction between activated glucocorticoid receptors and activated pro-inflammatory transcription factors, such as nuclear factor-kappa B and activator protein-1.4 Chronic inflammation is often characterized by enhanced expression of these transcription factors that bind to and activate coactivator molecules, which then acetylate core histones to switch on gene transcription to further amplify the inflammatory process.5 Corticosteroids suppress the multiple inflammatory gene expression by promoting histone deacetylation, resulting in tighter coiling of DNA and reduced access of transcription factors to their binding sites.4

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Humans
Absorption

Following oral inhalation of 320 mcg of beclomethasone dipropionate (BDP), the Cmax was 88 pg/mL and it was reached after 0.5 at post-administration. The mean Cmax of the major and most active metabolite, beclomethasone-17-monopropionate (17-BMP), was 1419 pg/mL at 0.7 hour post-dosing.11

In another pharmacokinetic study, the AUC of BDP and 17-BMP were 6660 and 6185 pgxh/mL, respectively. The Cmax was 35356 pg/mL for BDP and 2633 pg/mL for 17-BMP, and and the median time to reach these concentrations (Tmax) was 0.2 hours. In the same study, the AUC of 17-BMP following oral and intranasal administration were 10158 and 3660 pgxh/mL, respectively. The Cmax of 17-BMP following oral and intranasal administration were 703 and 310 pg/mL, respectively, and the Tmax was 4 hours. The total bioavailability of 17-BMP following oral and intranasal administration were 41% and 44%, respectively.1

Volume of distribution

Following intravenous administration, the steady-state volume of distribution was 20 L for beclomethasone dipropionate and 424 L for the active metabolite, beclomethasone-17-monopropionate.1

Protein binding

Based on the findings of in vitro studies, the protein binding of the main active metabolite, beclomethasone-17-monopropionate (17-BMP), was 94-96% over the concentration range of 1000 to 5000 pg/mL.11

Metabolism

During absorption, beclomethasone dipropionate is undergoes rapid and extensive hydrolysis mediated by esterases CYP3A to form beclomethasone-17-monopropionate (17-BMP), beclomethasone-21-monopropionate (21-BMP), and beclomethasone (BOH). 17-BMP is the major active metabolite with the most potent anti-inflammatory activity.11 About 95% of the total beclomethasone dipropionate administered via oral inhalation undergoes presystemic conversion to form 17-BMP in the lung.1

Hover over products below to view reaction partners

Route of elimination

Regardless of the route of administration, beclomethasone dipropionate and its metabolites are predominantly excreted in the feces, with less than 10% of the drug and its metabolites being excreted in the urine.11 12

Half-life

Following intravenous administration, the half life of beclomethasone dipropionate was 0.5 hours while the half life of the active metabolite 17-BMP was 2.7 hours. Following oral and intranasal administration, the half life of 17-BMP was 8.8 and 5.7 hours, respectively.1

Clearance

Following intravenous administration, the clearance of beclomethasone dipropionate and 17-BMP were 150 L/h and 120 L/h, respectively.1

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

The oral LD50 in rats is >3750 mg/kg.MSDS

The 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.

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
AbametapirThe serum concentration of Beclomethasone dipropionate can be increased when it is combined with Abametapir.
AbataceptThe risk or severity of adverse effects can be increased when Beclomethasone dipropionate is combined with Abatacept.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Beclomethasone dipropionate.
AcalabrutinibThe metabolism of Acalabrutinib can be increased when combined with Beclomethasone dipropionate.
AcarboseThe risk or severity of hyperglycemia can be increased when Beclomethasone dipropionate is combined with Acarbose.
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Beclomethasone dipropionate monohydrate4H7L9AI22I77011-63-3QHQJZIXSVLFOHD-LYRZEVDOSA-N
Active Moieties
NameKindUNIICASInChI Key
Beclomethasone 17-monopropionateprodrug5BGA9FD55H5534-18-9OHYGPBKGZGRQKT-XGQKBEPLSA-N
International/Other Brands
Aerobec (Teva) / Aldecin (Schering-Plough) / Anceron / Andion / Beclacin (Mayado Seiyaku) / Becloforte (GlaxoSmithKline) / Beclomet (Orion) / Beclorhinol (Chiesi) / Becloval / Beclovent (GlaxoSmithKline) / Becodisks (GlaxoSmithKline) / Beconase (GlaxoSmithKline) / Beconasol / Becotide (GlaxoSmithKline) / Clenil-A / Entyderma / Inalone (GlaxoSmithKline) / Korbutone / orBec (DOR BioPharma, Inc.) / Rino-Clenil (Chiesi) / Rivanase / Sanasthmax (Chiesi) / Sanasthmyl / Vancenase / Vanceril
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Beclodisk - Pwr Inh 100mcg/blisterPowder100 mcg / blisterRespiratory (inhalation)Glaxo Wellcome1997-09-032000-05-24Canada flag
Beclodisk - Pwr Inh 200mcg/blisterPowder200 mcg / blisterRespiratory (inhalation)Glaxo Wellcome1997-06-112000-05-24Canada flag
Beclodisk Pwr 100mcg/blisterPowder100 mcg / blisterRespiratory (inhalation)Glaxo Canada Inc1989-12-311998-07-30Canada flag
Beclodisk Pwr 200mcg/blisterPowder200 mcg / blisterRespiratory (inhalation)Glaxo Canada Inc1989-12-311998-07-30Canada flag
Becloforte 250mcg/aemAerosol, metered250 mcg / actRespiratory (inhalation)Glaxo Canada Inc1988-12-311998-07-30Canada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Alti-beclomethasone Dipropionate Inhaler 50mcg/mdAerosol, metered50 mcg / actRespiratory (inhalation)Altimed Pharma Inc.1992-12-312005-05-27Canada flag
Apo-beclomethasone Nasal SpraySuspension50 mcg / actNasalApotex Corporation1998-10-07Not applicableCanada flag
Mylan-beclo AQAerosol, metered; Suspension50 mcg / actNasalMylan Pharmaceuticals1995-12-31Not applicableCanada flag
Ratio-beclomethasone AQSpray50 mcg / actNasalRatiopharm Inc Division Of Teva Canada Limited1995-12-312010-05-21Canada flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
ALABASTERBeclomethasone dipropionate (200 mcg) + Formoterol fumarate (6 mcg)Aerosol, powderRespiratory (inhalation)Master Pharma S.R.L.2017-01-02Not applicableItaly flag
ALABASTERBeclomethasone dipropionate (200 mcg) + Formoterol fumarate (12 mcg)Powder, meteredRespiratory (inhalation)Master Pharma S.R.L.2020-09-09Not applicableItaly flag
ALABASTERBeclomethasone dipropionate (200 mcg) + Formoterol fumarate (6 mcg)Aerosol, powderRespiratory (inhalation)Master Pharma S.R.L.2017-01-02Not applicableItaly flag
ALABASTERBeclomethasone dipropionate (100 MICROGRAMMI) + Formoterol fumarate (6 mcg)PowderRespiratory (inhalation)Master Pharma S.R.L.2014-07-08Not applicableItaly flag
ALABASTERBeclomethasone dipropionate (100 MICROGRAMMI) + Formoterol fumarate (6 mcg)PowderRespiratory (inhalation)Master Pharma S.R.L.2020-03-14Not applicableItaly flag

Categories

ATC Codes
D07CC04 — Beclometasone and antibioticsR03AL09 — Formoterol, glycopyrronium bromide and beclometasoneR03BA01 — BeclometasoneD07AC15 — BeclometasoneR03AK08 — Formoterol and beclometasoneR03AK13 — Salbutamol and beclometasoneR01AD01 — BeclometasoneA07EA07 — Beclometasone
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
Steroid esters / 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Alpha-acyloxy ketones / Dicarboxylic acids and derivatives / Secondary alcohols / Carboxylic acid esters
show 7 more
Substituents
11-beta-hydroxysteroid / 11-hydroxysteroid / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 9-halo-steroid / Alcohol / Aliphatic homopolycyclic compound / Alkyl chloride / Alkyl halide
show 23 more
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
propanoate ester, enone, 11beta-hydroxy steroid, glucocorticoid, steroid ester, 20-oxo steroid, 3-oxo-Delta(1),Delta(4)-steroid, chlorinated steroid, corticosteroid (CHEBI:3002)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
5B307S63B2
CAS number
5534-09-8
InChI Key
KUVIULQEHSCUHY-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,3aS,3bS,9aS,9bR,10S,11aS)-9b-chloro-10-hydroxy-2,9a,11a-trimethyl-7-oxo-1-(propanoyloxy)-1H,2H,3H,3aH,3bH,4H,5H,7H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthren-1-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

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 References
  1. Daley-Yates PT, Price AC, Sisson JR, Pereira A, Dallow N: Beclomethasone dipropionate: absolute bioavailability, pharmacokinetics and metabolism following intravenous, oral, intranasal and inhaled administration in man. Br J Clin Pharmacol. 2001 May;51(5):400-9. doi: 10.1046/j.0306-5251.2001.01374.x. [Article]
  2. Brogden RN, Heel RC, Speight TM, Avery GS: Beclomethasone dipropionate. A reappraisal of its pharmacodynamic properties and therapeutic efficacy after a decade of use in asthma and rhinitis. Drugs. 1984 Aug;28(2):99-126. doi: 10.2165/00003495-198428020-00002. [Article]
  3. Edwards TB: Effectiveness and safety of beclomethasone dipropionate, an intranasal corticosteroid, in the treatment of patients with allergic rhinitis. Clin Ther. 1995 Nov-Dec;17(6):1032-41. [Article]
  4. Barnes PJ: Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci (Lond). 1998 Jun;94(6):557-72. [Article]
  5. Barnes PJ: How corticosteroids control inflammation: Quintiles Prize Lecture 2005. Br J Pharmacol. 2006 Jun;148(3):245-54. doi: 10.1038/sj.bjp.0706736. [Article]
  6. Grebe SK, Feek CM, Durham JA, Kljakovic M, Cooke RR: Inhaled beclomethasone dipropionate suppresses the hypothalamo-pituitary-adrenal axis in a dose dependent manner. Clin Endocrinol (Oxf). 1997 Sep;47(3):297-304. [Article]
  7. Dluhy RG: Clinical relevance of inhaled corticosteroids and HPA axis suppression. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 2):S447-50. [Article]
  8. Wilcox JB, Avery GS: Beclomethasone dipropionate corticosteroid inhaler: a preliminary report of its pharmacological properties and therapeutic efficacy in asthma. Drugs. 1973;6(2):84-93. doi: 10.2165/00003495-197306020-00002. [Article]
  9. Philip J: The effects of inhaled corticosteroids on growth in children. Open Respir Med J. 2014 Dec 31;8:66-73. doi: 10.2174/1874306401408010066. eCollection 2014. [Article]
  10. Rizzello F, Mazza M, Salice M, Calabrese C, Calafiore A, Campieri M, Gionchetti P: The safety of beclomethasone dipropionate in the treatment of ulcerative colitis. Expert Opin Drug Saf. 2018 Sep;17(9):963-969. doi: 10.1080/14740338.2018.1510914. Epub 2018 Aug 21. [Article]
  11. QVAR® (beclomethasone dipropionate HFA) for oral inhalation use - FDA Label [Link]
  12. BECONASE AQ® (beclomethasone dipropionate, monohydrate) for intranasal use only - FDA Label [Link]
  13. DIPROSONE® (Betamethasone Dipropionate Cream) - Product Monograph - Merck Canada Inc. [Link]
  14. DIPROLENE® (augmented betamethasone dipropionate) ointment, for topical use - FDA Label [Link]
Human Metabolome Database
HMDB0014538
KEGG Drug
D07495
KEGG Compound
C07813
PubChem Compound
21700
PubChem Substance
46509195
ChemSpider
20396
RxNav
1348
ChEBI
3002
ChEMBL
CHEMBL1200500
ZINC
ZINC000003938744
Therapeutic Targets Database
DAP000416
PharmGKB
PA448547
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Beclometasone
MSDS
Download (55.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableAsthma1
4CompletedPreventionBronchospasm / Respiratory Sounds / Respiratory Tract Infections (RTI)1
4CompletedPreventionSeasonal Allergic Rhinitis1
4CompletedTreatmentAcute Lymphocytic Leukemia, Pediatric / Asthma1
4CompletedTreatmentAllergic Rhinitis (AR)1

Pharmacoeconomics

Manufacturers
  • Glaxosmithkline
  • Schering corp sub schering plough corp
  • Schering corp
Packagers
  • 3M Health Care
  • A-S Medication Solutions LLC
  • Dispensing Solutions
  • GlaxoSmithKline Inc.
  • Graceway Pharmaceuticals
  • Medisca Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
Dosage Forms
FormRouteStrength
Powder, meteredRespiratory (inhalation)
AerosolBuccal0.989 mg
AerosolRespiratory (inhalation)100 mcg
Aerosol, meteredNasal
Aerosol, sprayRespiratory (inhalation)
AerosolRespiratory (inhalation)0.08287 g
PowderRespiratory (inhalation)100 mcg / blister
PowderRespiratory (inhalation)200 mcg / blister
SolutionBuccal; Respiratory (inhalation)0.25 mg
Aerosol, meteredRespiratory (inhalation)250 mcg / act
GasRespiratory (inhalation)100 UG
AerosolRespiratory (inhalation)0.329 g
AerosolRespiratory (inhalation)0.066 g
SprayNasal100 UG
Aerosol, powderRespiratory (inhalation)0.1 MG
Aerosol, powderRespiratory (inhalation)0.4 MG
Aerosol, powderRespiratory (inhalation)0.1 mg/1
Aerosol, powderRespiratory (inhalation)0.2 mg/1
Aerosol, powderRespiratory (inhalation)0.4 mg/1
Aerosol, powderRespiratory (inhalation)0.2 MG
Powder, meteredRespiratory (inhalation)180 mcg
PowderRespiratory (inhalation)200 mcg/1dose
PowderRespiratory (inhalation)
Spray, suspensionNasal50 mcg/1dose
Spray, meteredNasal50 MCG
SprayNasal0.05 MG
SprayNasal0.10 MG
GasRespiratory (inhalation)200 UG
GasRespiratory (inhalation)0.05 MG
GasRespiratory (inhalation)0.10 MG
GasRespiratory (inhalation)0.20 MG
GasRespiratory (inhalation)0.25 MG
SprayNasal50 UG
SuspensionRespiratory (inhalation)0.025 mg
SuspensionRespiratory (inhalation)10 mg
SolutionRespiratory (inhalation)50 mcg
SuspensionRespiratory (inhalation)0.011 g
SuspensionRespiratory (inhalation)0.01 g
SuspensionRespiratory (inhalation)0.062 % w/v
SuspensionRespiratory (inhalation)0.329 g
AerosolRespiratory (inhalation)50 mcg
AerosolIntrasinal0.07 %
AerosolRespiratory (inhalation)0.07 %
SolutionRespiratory (inhalation)0.09549 % w/w
AerosolRespiratory (inhalation)10 mg
AerosolRespiratory (inhalation)89.29 g
Aerosol, meteredRespiratory (inhalation)100 MICROGRAMMI
Aerosol, meteredRespiratory (inhalation)200 MICROGRAMMI
Aerosol, meteredRespiratory (inhalation)250 MICROGRAMMI
Aerosol, meteredRespiratory (inhalation)50 MICROGRAMMI
SuspensionRespiratory (inhalation)400 MICROGRAMMI
SuspensionRespiratory (inhalation)800 MICROGRAMMI
Aerosol, meteredNasal; Respiratory (inhalation)50 mcg / act
SuspensionNasal50 mcg / act
AerosolRespiratory (inhalation)0.328 % w/w
AerosolRespiratory (inhalation)0.06579 g
AerosolRespiratory (inhalation)0.0658 % w/w
AerosolRespiratory (inhalation)0.08 % w/w
CreamTopical
SuspensionRespiratory (inhalation)
SuspensionIntrasinal; Nasal0.05 g
SprayNasal0.05 mg/0.13mL
SuspensionNasal; Respiratory (inhalation)51.73 mcg
SuspensionRespiratory (inhalation)0.32895 % w/w
AerosolRespiratory (inhalation)0.06579 % w/v
SolutionRespiratory (inhalation)0.06579 % w/v
CapsuleRespiratory (inhalation)100 mcg / cap
CapsuleRespiratory (inhalation)200 mcg / cap
SuspensionRectal
Tablet, delayed releaseOral
SprayNasal50 mcg/1dose
Spray, suspensionNasal42 ug/1
Spray, meteredNasal
Aerosol, meteredNasal50 mcg / act
Aerosol, meteredRespiratory (inhalation)10 MG
SprayNasal10 ML
Spray, suspensionRespiratory (inhalation)200 MICROGRAMMI/ML
AerosolRespiratory (inhalation)
Spray, suspensionNasal100 mcg
CreamTopical0.025 %
OintmentTopical0.025 %
CreamTopical15 g
CreamTopical5 g
SuspensionRespiratory (inhalation)0.0832 g
Aerosol, meteredRespiratory (inhalation)200 MCG
Powder, meteredRespiratory (inhalation)100 MCG
Powder, meteredRespiratory (inhalation)400 MCG
AerosolRespiratory (inhalation)0.5 g
AerosolRespiratory (inhalation)0.1 %
LotionTopical
CreamCutaneous
CreamTopical0.025 % w/w
AerosolBuccal0.8475 mg
AerosolRespiratory (inhalation)50 cg
SuspensionRespiratory (inhalation)50 mg
PowderRespiratory (inhalation)100 MICROGRAMMI
PowderRespiratory (inhalation)200 MICROGRAMMI
PowderRespiratory (inhalation)400 MICROGRAMMI
SprayNasal30 ML
SuspensionRespiratory (inhalation)400 mcg/ml
SprayNasal250 mcg/1dose
AerosolRespiratory (inhalation)250 mcg
Aerosol; suspensionRespiratory (inhalation)
Spray, suspensionRespiratory (inhalation)
AerosolRespiratory (inhalation)
Aerosol, meteredRespiratory (inhalation)250 mcg
SolutionRespiratory (inhalation)250 cg
SolutionRespiratory (inhalation)50 cg
Aerosol; suspensionRespiratory (inhalation)50 MCG
SuspensionRespiratory (inhalation)0.800 mg
SuspensionRectal3 MG/60ML
Tablet, delayed releaseOral5 MG
AerosolBuccal0.859 mg
CreamTopical
CapsuleRespiratory (inhalation)0.1 mg/1
CapsuleRespiratory (inhalation)0.2 mg/1
CapsuleRespiratory (inhalation)0.4 mg/1
SprayNasal50 mcg
OintmentTopical
AerosolRespiratory (inhalation)0.07 % w/w
SolutionRespiratory (inhalation)0.42 % w/w
Aerosol, sprayRespiratory (inhalation)
CapsuleRespiratory (inhalation)
GasRespiratory (inhalation)
SolutionRespiratory (inhalation)
Aerosol, powderRespiratory (inhalation)
Powder, meteredRespiratory (inhalation)
Powder, meteredRespiratory (inhalation)100 mcg
Aerosol, meteredRespiratory (inhalation)0.100 mg
AerosolBuccal0.833 mg
Aerosol, meteredRespiratory (inhalation)
Aerosol, meteredRespiratory (inhalation)
SprayNasal
AerosolBuccal
Aerosol, metered; solutionRespiratory (inhalation)
Drug delivery systemBuccal
PowderRespiratory (inhalation)
GasRespiratory (inhalation)50 UG
Aerosol, foamRectal3 MG
LotionCutaneous
LotionTopical0025 %
OintmentCutaneous
OintmentTopical0.25 mg/g
OintmentTopical30 G
SolutionTopical
CreamTopical0.25 MG/G
OintmentTopical0025 %
SolutionCutaneous; Topical0.25 MG/G
CreamTopical0025 %
AerosolBuccal0.4347 g
Aerosol, metered; suspensionNasal50 mcg / act
SolutionRespiratory (inhalation)250 mcg
Spray, suspensionRespiratory (inhalation)0.04 %
CreamTopical0.025 % w/w
CreamTopical.025 %
LotionTopical.025 %
LotionTopical0.025 %
Aerosol, meteredNasal40 mcg / act
Aerosol, meteredNasal40 ug/1
Aerosol, meteredNasal80 ug/1
Aerosol, meteredNasal80 mcg / act
Aerosol, meteredRespiratory (inhalation)100 mcg / act
Aerosol, meteredRespiratory (inhalation)40 ug/1
Aerosol, meteredRespiratory (inhalation)50 mcg / act
Aerosol, meteredRespiratory (inhalation)80 ug/1
Aerosol, meteredRespiratory (inhalation)100 mcg
Aerosol, meteredRespiratory (inhalation)50 mcg
SprayNasal50 mcg / act
SprayNasal0.1 MG
SolutionNasal77.00 mg
SprayNasal100 MCG
AerosolRespiratory (inhalation)0.1 g
SuspensionIntrasinal; Nasal0.0505 g
GasRespiratory (inhalation)250 UG
GasRespiratory (inhalation)50 µg
Aerosol, foamRectal42 MG
Suppository3 MG
SuspensionRectal3 MG
AerosolRespiratory (inhalation)0.1497 g
AerosolRespiratory (inhalation)0.3743 g
AerosolBuccal0.0588 g
AerosolRespiratory (inhalation)250 mcg/1dose
Aerosol, meteredRespiratory (inhalation)50 mcg/1dose
Spray, suspensionNasal100 mcg/1dose
AerosolRespiratory (inhalation)100 mcg/1dose
AerosolRespiratory (inhalation)200 mcg/1dose
AerosolRespiratory (inhalation)50 mcg/1dose
Prices
Unit descriptionCostUnit
Beconase AQ 42 mcg/spray Suspension 25 gm Inhaler149.32USD inhaler
Beclomethasone dipro powder107.1USD g
Qvar 80 mcg/act Aerosol 7.3 gm Inhaler105.64USD inhaler
Qvar 40 mcg/act Aerosol 7.3 gm Inhaler87.5USD inhaler
Qvar 80 mcg inhaler19.05USD g
Qvar 40 mcg inhaler15.12USD g
Propaderm 250 mcg/g Cream0.46USD g
Qvar Cfc-Free 100 mcg/dose Metered Dose Aerosol0.33USD dose
Qvar Cfc-Free 50 mcg/dose Metered Dose Aerosol0.16USD dose
Apo-Beclomethasone 50 mcg/dose Metered Dose Spray0.06USD dose
Mylan-Beclo Aq. 50 mcg/dose Metered Dose Spray0.06USD dose
Nu-Beclomethasone 50 mcg/dose Metered Dose Spray0.06USD dose
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5776432No1998-07-072015-07-07US flag
US6446627No2002-09-102017-12-18US flag
US8132712No2012-03-132028-09-07US flag
US7780038No2010-08-242027-01-24US flag
US9463289No2016-10-112031-05-18US flag
US8931476No2015-01-132031-07-17US flag
US7637260No2009-12-292020-08-25US flag
US9808587No2017-11-072031-05-18US flag
US10022510Yes2018-07-172031-11-18US flag
US10022509No2018-07-172031-05-18US flag
US10086156No2018-10-022031-05-18US flag
US10188811No2019-01-292031-10-21US flag
US10561808Yes2020-02-182032-07-01US flag
US10695512No2020-06-302031-05-18US flag
US10792447No2020-10-062039-01-25US flag
US11395889No2011-05-182031-05-18US flag
US11395888No2018-01-262038-01-26US flag
US11559637No2019-07-212039-07-21US flag
US11583643No2021-08-192041-08-19US flag
US11793953No2018-01-262038-01-26US flag
US11865247No2018-01-262038-01-26US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)208-210MSDS
logP3.49MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.00208 mg/mLALOGPS
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 Area106.97 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity134.79 m3·mol-1Chemaxon
Polarizability54.46 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9904
Blood Brain Barrier+0.9851
Caco-2 permeable+0.5698
P-glycoprotein substrateSubstrate0.7529
P-glycoprotein inhibitor IInhibitor0.5986
P-glycoprotein inhibitor IINon-inhibitor0.7488
Renal organic cation transporterNon-inhibitor0.7907
CYP450 2C9 substrateNon-substrate0.8634
CYP450 2D6 substrateNon-substrate0.9174
CYP450 3A4 substrateSubstrate0.784
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.7516
CYP450 2C19 inhibitorNon-inhibitor0.9122
CYP450 3A4 inhibitorNon-inhibitor0.7875
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8577
Ames testNon AMES toxic0.938
CarcinogenicityNon-carcinogens0.914
BiodegradationNot ready biodegradable0.9932
Rat acute toxicity2.1115 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9456
hERG inhibition (predictor II)Non-inhibitor0.6054
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11.1 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00pi-7931200000-ebf9cfbf75bf09c67c7a
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000f-0930000000-081eac0a05abab8fc5fa
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000f-0930000000-081eac0a05abab8fc5fa
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0a4i-3920000000-d6e2b1ac89621299e6bb
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0536-0000390000-d1146b326a2bf27937e3
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-0489240000-9581961e5dddfb7a403f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0h71-3892000000-454fb634c4339a1ebfe0
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-024l-0008920000-a205fd9109c2f6812157
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9000100000-76f5ed00ded16971a794
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-022a-0226930000-a00f9623df7b67c42501
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9001000000-c649a4588e91f0c3fee5
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01bj-1954800000-552c0475a01c181caff3
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-9000000000-5cce3b96400ce51934c9
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-229.3158221
predicted
DarkChem Lite v0.1.0
[M-H]-207.07243
predicted
DeepCCS 1.0 (2019)
[M+H]+230.2261221
predicted
DarkChem Lite v0.1.0
[M+H]+209.02943
predicted
DeepCCS 1.0 (2019)
[M+Na]+229.3366221
predicted
DarkChem Lite v0.1.0
[M+Na]+215.17845
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Humans
Pharmacological action
Yes
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. Saklatvala J: Glucocorticoids: do we know how they work? Arthritis Res. 2002;4(3):146-50. Epub 2002 Jan 21. [Article]
  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. [Article]
  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. [Article]
  4. Wurthwein G, Rohdewald P: Activation of beclomethasone dipropionate by hydrolysis to beclomethasone-17-monopropionate. Biopharm Drug Dispos. 1990 Jul;11(5):381-94. [Article]

Enzymes

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. Hukkanen J, Vaisanen T, Lassila A, Piipari R, Anttila S, Pelkonen O, Raunio H, Hakkola J: Regulation of CYP3A5 by glucocorticoids and cigarette smoke in human lung-derived cells. J Pharmacol Exp Ther. 2003 Feb;304(2):745-52. [Article]
  2. Roberts JK, Moore CD, Ward RM, Yost GS, Reilly CA: Metabolism of beclomethasone dipropionate by cytochrome P450 3A enzymes. J Pharmacol Exp Ther. 2013 May;345(2):308-16. doi: 10.1124/jpet.112.202556. Epub 2013 Mar 19. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
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. Roberts JK, Moore CD, Ward RM, Yost GS, Reilly CA: Metabolism of beclomethasone dipropionate by cytochrome P450 3A enzymes. J Pharmacol Exp Ther. 2013 May;345(2):308-16. doi: 10.1124/jpet.112.202556. Epub 2013 Mar 19. [Article]
  2. Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]

Carriers

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. 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. [Article]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]

Transporters

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. Crowe A, Tan AM: Oral and inhaled corticosteroids: differences in P-glycoprotein (ABCB1) mediated efflux. Toxicol Appl Pharmacol. 2012 May 1;260(3):294-302. doi: 10.1016/j.taap.2012.03.008. Epub 2012 Mar 23. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Pavek P, Merino G, Wagenaar E, Bolscher E, Novotna M, Jonker JW, Schinkel AH: Human breast cancer resistance protein: interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther. 2005 Jan;312(1):144-52. doi: 10.1124/jpet.104.073916. Epub 2004 Sep 13. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. de Graan AJ, Lancaster CS, Obaidat A, Hagenbuch B, Elens L, Friberg LE, de Bruijn P, Hu S, Gibson AA, Bruun GH, Corydon TJ, Mikkelsen TS, Walker AL, Du G, Loos WJ, van Schaik RH, Baker SD, Mathijssen RH, Sparreboom A: Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel. Clin Cancer Res. 2012 Aug 15;18(16):4433-40. doi: 10.1158/1078-0432.CCR-12-0761. Epub 2012 Jun 18. [Article]
  2. Gui C, Obaidat A, Chaguturu R, Hagenbuch B: Development of a cell-based high-throughput assay to screen for inhibitors of organic anion transporting polypeptides 1B1 and 1B3. Curr Chem Genomics. 2010 Mar 1;4:1-8. doi: 10.2174/1875397301004010001. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. de Graan AJ, Lancaster CS, Obaidat A, Hagenbuch B, Elens L, Friberg LE, de Bruijn P, Hu S, Gibson AA, Bruun GH, Corydon TJ, Mikkelsen TS, Walker AL, Du G, Loos WJ, van Schaik RH, Baker SD, Mathijssen RH, Sparreboom A: Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel. Clin Cancer Res. 2012 Aug 15;18(16):4433-40. doi: 10.1158/1078-0432.CCR-12-0761. Epub 2012 Jun 18. [Article]
  2. Gui C, Obaidat A, Chaguturu R, Hagenbuch B: Development of a cell-based high-throughput assay to screen for inhibitors of organic anion transporting polypeptides 1B1 and 1B3. Curr Chem Genomics. 2010 Mar 1;4:1-8. doi: 10.2174/1875397301004010001. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48