In 16HBE cells, beclometasone dipropionate (1-100 nM; 20 min) decreases the amounts of NT, ROS, and iNOS produced by rhIL-17A as well as STAT-1 expression[2].

Beclometasone dipropionate (150 µg/kg; nebulization; male BALB/c mice) reduces the relative eosinophil number and total cell count while relieving asthma[1].

Western Blot Analysis[2]
Cell Types: 16HBE cells
Tested Concentrations: 1, 10 and 100 nM
Incubation Duration: 20 min
Experimental Results: decreased the levels of iNOS, ROS and NT generated by rhIL-17A.

Animal/Disease Models: Tenweeks old male balb/c (Bagg ALBino) mouse[2].
Doses: 5 mg/kg (100 μg/ml for 60 min).
Route of Administration: Orally at 24 h and 1 h before the LPS aerosol.
Experimental Results: Dramatically (P < 0.05) inhibited the decrease of IL-10 level in BAL fluid induced by LPS exposure. Markedly decreased the release of both MMP-2 and MMP-9.

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Animal/Disease Models: Male balb/c (Bagg ALBino) mouse with asthma[1]
Doses: 150 µg/kg
Route of Administration: Nebulization
Experimental Results: diminished total cell number and relative eosinophil number in BALF .

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

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Metabolism / Metabolites
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. About 95% of the total beclomethasone dipropionate administered via oral inhalation undergoes presystemic conversion to form 17-BMP in the lung.

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Biological 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.

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.

[1]. Applicability of an ultrasonic nebulization system for the airways delivery of beclomethasone dipropionate in a murine model of asthma. Pharm Res. 2006 Aug;23(8):1765-75.

[2]. Beclomethasone dipropionate and formoterol reduce oxidative/nitrosative stress generated by cigarette smoke extracts and IL-17A in human bronchial epithelial cells. Eur J Pharmacol. 2013 Oct 15;718(1-3):418-27.

Beclomethasone Dipropionate can cause developmental toxicity according to state or federal government labeling requirements.
Beclomethasone dipropionate is a steroid ester comprising beclomethasone having propionyl groups at the 17- and 21-positions. It has a role as an anti-inflammatory drug, an anti-asthmatic drug, a prodrug and an anti-arrhythmia drug. It is a steroid ester, an enone, a 20-oxo steroid, an 11beta-hydroxy steroid, a propanoate ester, a corticosteroid, a glucocorticoid, a 3-oxo-Delta(1),Delta(4)-steroid and a chlorinated steroid. It is functionally related to a beclomethasone.
Beclomethasone dipropionate is a second-generation synthetic corticosteroid and diester of beclomethasone, which is structurally similar to [dexamethasone]. It is a prodrug of an active metabolite beclomethasone 17-monopropionate (17-BMP) 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. 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. 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. 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.
Beclomethasone Dipropionate is the dipropionate ester of a synthetic glucocorticoid with anti-inflammatory and immunomodulating properties. After cell surface receptor attachment and cell entry, beclomethasone enters the nucleus where it binds to and activates specific nuclear receptors, resulting in an altered gene expression and inhibition of proinflammatory cytokine production.
An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of ASTHMA.
See also: Beclomethasone (has active moiety); Beclomethasone 17-Monopropionate (has active moiety); Beclomethasone Dipropionate Monohydrate (annotation moved to).

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Drug 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. 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. Indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses in patients 13 years of age and older. 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.

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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. 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. 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. 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. 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. 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.

C28H37CLO7

521.04

520.222

5534-09-8

Betamethasone dipropionate;5593-20-4;Beclometasone dipropionate-d10;Beclometasone;4419-39-0;Beclometasone dipropionate-d6;Beclometasone dipropionate monohydrate;77011-63-3

21700

White to off-white solid powder

1.3±0.1 g/cm3

630.5±55.0 °C at 760 mmHg

210ºC

335.1±31.5 °C

0.0±4.2 mmHg at 25°C

1.564

4.59

1

7

8

36

1050

8

CCC(=O)OCC(=O)[C@]1([C@H](C[C@@H]2[C@@]1(C[C@@H]([C@]3([C@H]2CCC4=CC(=O)C=C[C@@]43C)Cl)O)C)C)OC(=O)CC

KUVIULQEHSCUHY-XYWKZLDCSA-N

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

(8S,9R,10S,11S,13S,14S,16S,17R)-9-chloro-11-hydroxy-10,13,16-trimethyl-3-oxo-17-[2-(propionyloxy)acetyl]-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-17-yl propionate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)